scholarly journals How does displacement of albumin-bound tryptophan cause sustained increases in the free tryptophan concentration in plasma and 5-hydroxytryptamine synthesis in brain?

1989 ◽  
Vol 262 (1) ◽  
pp. 365-368 ◽  
Author(s):  
M Salter ◽  
R G Knowles ◽  
C I Pogson
Keyword(s):  
Serum Albumin ◽  
Transit Time ◽  
Rapid Rate ◽  
Free Tryptophan ◽  
Tryptophan Catabolism ◽  
Tryptophan Concentration ◽  
The Brain ◽  
Sustained Increase

Models of tryptophan catabolism and binding to serum albumin are presented to explain the observed effect of displacement of tryptophan from albumin on the concentrations of free and bound tryptophan and on the rate of 5-hydroxytryptamine (5-HT) synthesis from tryptophan in the brain. A rapid rate of dissociation of tryptophan from albumin (compared to the transit time of tryptophan through the liver) and a large fractional extraction of the free pool of tryptophan during passage through the liver are shown to be necessary factors in determining the effects observed. Because of the low fractional extraction of free tryptophan in the brain, the synthesis of 5-HT will be dependent only upon the free pool of tryptophan. Dissociation of tryptophan from albumin only causes a sustained increase in 5-HT synthesis in the brain because of the effect that this dissociation has on hepatic tryptophan catabolism and thereby on the free pool of tryptophan.

scholarly journals The effects of diet, lipolysis and limb ischaemia on the distribution of plasma tryptophan in the rat

1975 ◽  
Vol 146 (3) ◽  
pp. 659-666 ◽  
Author(s):  
H B Stoner ◽  
V J Cunningham ◽  
P M Elson ◽  
A Hunt
Keyword(s):  
Fatty Acid ◽  
Acid Concentration ◽  
Fatty Acid Concentration ◽  
Limb Ischaemia ◽  
Plasma Tryptophan ◽  
Free Tryptophan ◽  
Esterified Fatty Acids ◽  
Tryptophan Concentration ◽  
Free Plasma ◽  
Sustained Increase

A non-linear relationship between the plasma non-esterified fatty acid concentration and the percentage of free plasma tryptophan was found in rats in different nutritional states, although non-esterified fatty acids are not the only factors determining the percentage of free tryptophan. This relationship was not seen in rats injured by limb ischaemia. The effect of drugs causing rapid increases in the plasma non-esterified fatty acid concentration was also studied. Isoprenaline decreased the total plasma tryptophan concentration. Dichloroisoprenaline caused a sustained increase in the plasma non-esterified fatty acid concentration which was accompanied by an increase in the concentration of free plasma tryptophan and followed by a fall in the concentration of total tryptophan. The loss of tryptophan from the plasma was attributed to an altered distribution of tryptophan in the extracellular space rather than to increased metabolism. This interpretation was supported by determinations of the irreversible disposal rate of plasma tryptophan which in uninjured rats was unaffected by the concentration of free plasma tryptophan. In the injured rats this rate was unaltered during limb ischaemia but was decreased after removal of the tourniquets; increased competition for tissue entry by other neutral amino acids and the fall in body temperature could be factors in this fall.

The Daily Rhythm of Plasma Tryptophan and Tyrosine in Depression

1976 ◽  
Vol 128 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Pekka Niskanen ◽  
Matti Huttunen ◽  
Tapani Tamminen ◽  
Juha Jääskeläinen
Keyword(s):  
Control Group ◽  
Total Plasma ◽  
Plasma Tryptophan ◽  
Free Tryptophan ◽  
The Times ◽  
Plasma Tyrosine ◽  
Depressive Patients ◽  
The Brain ◽  
Free Plasma ◽  
Tryptophan Level

SummaryThe study dealt with the level of and diurnal alterations in the concentration of tryptophan, free tryptophan and tyrosine in the blood plasma of 20 inhibited depression patients and 10 healthy controls.The results suggested that there was no distinct relationship between either the total plasma tryptophan or plasma tyrosine level and depression. On the other hand, the free plasma tryptophan level was, at all the times of day at which measurements were made, either significantly or almost significantly higher in the patients than in the controls. It was further found that the results of measurement were related to the patients’ clinical improvement, as measured by the Hamilton test, in such a way that after four weeks of treatment the free plasma tryptophan level in ‘poorly improved’ patients continued to be significantly higher in comparison with the controls, whereas the values for the ‘well improved’ patient group did not differ greatly from the corresponding values for the control group any longer.It may be hypothesized that the rise in the free plasma tryptophan in depressive patients might represent an effort made by the peripheral body to compensate for the slowed-up serotonin metabolism of the brain, whereby the tryptophan mobilized from the periphery would serve as a sort of ‘endogenous antidepressant’ provided by the organism itself.

Abstract 1382: AlbuBNP (Cardeva), a Novel Recombinant Human B-Type Natriuretic Peptide Serum Albumin Fusion Protein Has Prolonged Renal Enhancing Properties When Compared to Human BNP.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Horng H Chen ◽  
Fernando L Matrin ◽  
Alessandro Cataliotti ◽  
John A Schirger ◽  
John C Burnett
Keyword(s):  
Fusion Protein ◽  
Serum Albumin ◽  
Single Molecule ◽  
Therapeutic Potential ◽  
Renal Diseases ◽  
Elimination Half ◽  
Sustained Reduction ◽  
Anesthetized Dogs ◽  
Long Acting ◽  
Sustained Increase

BACKGROUND: AlbuBNP is a novel recombinant human BNP serum albumin fusion protein which possesses a significantly longer elimination half-life compared to BNP. To date, it remains unclear if this novel protein which represents a single molecule of BNP synthesized with the carrier protein albumin can enter the post glomerular/tubular system due to the fusion of BNP to albumin and mediate renal actions. We hypothesized that this fusion protein will have potent renal actions and possess prolonged renal hemodynamic enhancing and excretory properties based upon its unique structure as compared to native BNP. METHODS: We compared the cardiorenal and humoral actions of intravenous(IV) bolus of administration of AlbuBNP (Cardeva, CoGenesys, Rockville MD) (5 mg/kg, n=7) and Human BNP (Phoenix Pharmaceutical, Belmont CA) (25 μ g/Kg, n=5) in two groups of normal anesthetized dogs. * p<0.05 RESULTS: Single IV bolus of AlbuBNP resulted in a sustained increase in plasma cGMP (5±1 to 9±2 pmol/ml*) and urinary cGMP excretion (1136±113 to 2556±417 pmol/min*), markers of the biological activity of BNP, which remained elevated at the termination of the experiment at 270 minutes. In contrast, with human BNP, both plasma and urinary cGMP peaked at 30 minutes and returned to baseline by 150 minutes. In a similar fashion, there was a sustained increase in natriuresis (39±12 to 159±38 μEq/min*), diuresis (0.2±0.1 to 1.1±0.3 ml/min*), renal blood flow (220±22 to 301±33 ml/min*), and glomerular filtration rate (34±2 to 62±13 ml/min*) with AlbuBNP while with human BNP, these renal effects peaked at 30 minutes and returned to baseline by 150 minutes. Furthermore, there was a gradual and sustained suppression of plasma aldosterone (7.8±2 to 3.6±1 ng/dL*) with AlbuBNP. Likewise, there was a more sustained reduction of cardiac filling pressures with AlbuBNP as compared to human BNP. CONCLUSION: We report for the first time that this newly developed BNP/albumin fusion protein has a more prolonged and sustained renal enhancing properties compared to human BNP. Thus, AlbuBNP (Cardeva) represents a novel long-acting renal enhancing and aldosterone suppressing drug which has therapeutic potential for the management of cardiovascular and renal diseases that should be defined in further studies.

Entry of CART into brain is rapid but not inhibited by excess CART or leptin

1999 ◽  
Vol 277 (5) ◽  
pp. E901-E904 ◽  
Author(s):  
Abba J. Kastin ◽  
Victoria Akerstrom
Keyword(s):  
Endothelial Cells ◽  
Regression Analysis ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Multiple Time ◽  
Rapid Rate ◽  
Efflux System ◽  
Anorectic Agent ◽  
The Brain

Cocaine- and amphetamine-regulated transcript (CART) is a new anorectic peptide found in the brain and periphery. It is closely associated with leptin, an anorectic agent saturably transported across the blood-brain barrier (BBB). Using multiple time-regression analysis, we found that CART has a rapid rate of entry into brain from blood. However, there was no self-inhibition with CART, even when perfused in blood-free buffer or in fasted mice, showing a lack of saturation. HPLC showed that at least 58% of the injected CART reached brain tissue in intact form, and capillary depletion with and without washout showed that the CART was not bound to endothelial cells or adherent to vascular components. There was no evidence for an efflux system out of the brain for CART. Thus CART can cross the BBB from blood to brain, but its rapid rate of entry is not inhibited by excess CART or leptin.

Basic Oscillating Mechanism of Cheyne-Stokes Breathing

1956 ◽  
Vol 187 (2) ◽  
pp. 395-398 ◽  
Author(s):  
Arthur C. Guyton ◽  
Jack W. Crowell ◽  
John W. Moore
Keyword(s):  
Carbon Dioxide ◽  
Control System ◽  
Transit Time ◽  
Perfusion Pressure ◽  
Respiratory Control ◽  
Delay System ◽  
Carbon Dioxide Concentrations ◽  
Respiratory Centers ◽  
Cheyne Stokes Breathing ◽  
The Brain

Cheyne-Stokes breathing has been induced in 30 dogs by inserting a circulatory delay system between the heart and the brain to prolong the transit time of blood from the lungs to the brain. The duration of each cycle of Cheyne-Stokes breathing increased proportionately with the volume of the delay system and decreased as the perfusion pressure to the brain was increased. Periodic variations in oxygen and carbon dioxide concentrations in the blood were found to be in appropriate phase to stimulate the respiratory centers at the time of maximal ventilation. This supports the theory that Cheyne-Stokes breathing is due to oscillation of the respiratory control system.

scholarly journals Contrast Enhancement of the Brain by Folate-Conjugated Gadolinium–Diethylenetriaminepentaacetic Acid–Human Serum Albumin Nanoparticles by Magnetic Resonance Imaging

2012 ◽  
Vol 11 (4) ◽  
pp. 7290.2011.00047 ◽  
Author(s):  
Huedayi Korkusuz ◽  
Karsten Ulbrich ◽  
Verena Bihrer ◽  
Katerina Welzel ◽  
Valery Chernikov ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Contrast Agents ◽  
Diethylenetriaminepentaacetic Acid ◽  
Resonance Imaging ◽  
Mri Contrast ◽  
The Brain ◽  
Signal Intensities

Different from regular small molecule contrast agents, nanoparticle-based contrast agents have a longer circulation time and can be modified with ligands to confer tissue-specific contrasting properties. We evaluated the tissue distribution of polymeric nanoparticles (NPs) prepared from human serum albumin (HSA), loaded with gadolinium–diethylenetriaminepentaacetic acid (Gd-DTPA) (Gd-HSA-NP), and coated with folic acid (FA) (Gd-HSA-NP-FA) in mice by magnetic resonance imaging (MRI). FA increases the affinity of the Gd-HSA-NP to FA receptor–expressing cells. Clinical 3 T MRI was used to evaluate the signal intensities in the different organs of mice injected with Gd-DTPA, Gd-HSA-NP, or Gd-HSA-NP-FA. Signal intensities were measured and standardized by calculating the signal to noise ratios. In general, the NP-based contrast agents provided stronger contrasting than Gd-DTPA. Gd-HSA-NP-FA provided a significant contrast enhancement (CE) in the brain ( p = .0032), whereas Gd-DTPA or Gd-HSA-NP did not. All studied MRI contrast agents showed significant CE in the blood, kidney, and liver ( p < .05). Gd-HSA-NP-FA elicited significantly higher CE in the blood than Gd-HSA-NP ( p = .0069); Gd-HSA-NP and Gd-HSA-NP-FA did not show CE in skeletal muscle and gallbladder; Gd-HSA-NP, but not Gd-HSA-NP-FA, showed CE in the cardiac muscle. Gd-HSA-NP-FA has potential as an MRI contrast agent in the brain.

scholarly journals ACCUMULATION OF ANTIBODIES IN THE CENTRAL NERVOUS SYSTEM

1930 ◽  
Vol 51 (6) ◽  
pp. 889-902 ◽  
Author(s):  
Jules Freund
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Slow Rate ◽  
Immune Serum ◽  
Brain Extract ◽  
Rapid Rate ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

1. Antibodies can be extracted from the brain and spinal cord of rabbits actively or passively immunized with typhoid bacilli. 2. The titers of the antibodies in the extracts of brain and cord depend upon the titer of the blood serum. In actively immunized rabbits the following numerical relationships exist between the titers of the serum and of these organ extracts: The ratio of the titer of the serum is to the titers of extract of brain and of the spinal cord about as 100 is to 0.8; the titer of the serum is to the titer of the cerebrospinal fluid as 100 is to 0.3. In passively immunized rabbits the titer of the serum is to the titer of brain and spinal-cord extract as 100 is to 0.7. 3. The antibodies recovered from the brain are not due to the presence of blood in it for perfusion of the brain does not reduce its antibody content appreciably. 4. Antibodies penetrate into the spinal fluid from the blood even in the absence of inflammation of the meninges. When the penetration is completed the following numerical relationship exists between the titer of the serum and that of the cerebrospinal fluid: 100 to 0.25. 5. The penetration into the cerebrospinal fluid of antibodies injected intravenously proceeds at a slow rate, being completed only several hours after the immune serum has been injected. The penetration of antibodies into the tissue of the brain occurs at a very rapid rate. It is completed within 15 minutes. 6. It is very unlikely that when the immune serum is injected intravenously the antibodies reach the brain tissue by way of the cerebrospinal fluid, for (1) the antibody titer of the cerebrospinal fluid is lower than that of the brain extract, and (2) antibodies penetrate faster into the tissue of the brain than into the cerebrospinal fluid.

Plasma free tryptophan concentration in autistic Children

1986 ◽  
Vol 8 (4) ◽  
pp. 424-427 ◽  
Author(s):  
Yoshihiko Hoshino ◽  
Toshiaki Yamamoto ◽  
Motohisa Kaneko ◽  
Hisashi Kumashiro
Keyword(s):  
Autistic Children ◽  
Free Tryptophan ◽  
Tryptophan Concentration

Population characteristics and prognostic factors in metastatic non-small cell lung cancer (NSCLC): The Fox Chase Cancer Center (FCCC) experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7644-7644
Author(s):  
V. Paralkar ◽  
T. Li ◽  
C. J. Langer
Keyword(s):  
Prognostic Factors ◽  
Serum Albumin ◽  
Performance Status ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Stage Iv ◽  
Cranial Irradiation ◽  
Population Characteristics ◽  
Cancer Center ◽  
The Brain

7644 Background: With increasing use of MRI and PET to stage NSCLC, the demographics, performance status and distribution of metastases at diagnosis in this patient (pt) population are changing; it is important to reassess the prognostic roles played by baseline clinical variables in the modern therapeutic era. Methods: We retrospectively evaluated the charts of 189 consecutive, unselected pts with stage IV NSCLC seen and followed at the Fox Chase Cancer Center between Oct 2000 and Aug 2003. Data on a variety of pt variables including demographics, histology, metastases, key laboratory tests and treatment were compiled. We intended to identify those that played statistically significant prognostic roles. Results: Median age at diagnosis was 62 years; 77% of pts had PS 0–1 at first presentation. 58% had single organ metastasis; 35% had metastases to the brain (half of these had brain only and a third had solitary brain metastasis). 51% of all pts received palliative radiation to the brain at some point after dx. Overall median survival was 10.8 months. The 1-yr, 2-yr, 3-yr and 4-yr overall survival rates were 44.2%, 21.9%, 11.6% and 7.8% respectively. On multivariate analysis, statistically significant negative prognostic factors included PS ≥ 2 (HR: 1.9, 95% CI: 1.1–3.3), serum albumin ≤ 3 (HR: 1.7, 95% CI: 1.1–2.8) and metastases to > 1 organ (HR: 1.6, 95% CI: 1.03–2.3). Bone and liver metastases, though associated with worse survival in univariate analysis, were not found to be independent predictors of survival. Gender had no bearing on outcome. Conclusions: Survival rates in this advanced NSCLC cohort equal or exceed contemporaneous ECOG figures. PS, serum albumin and number of organs with metastases are independent prognostic factors in NSCLC. The increasing detection of brain metastases at 1st presentation of metastatic NSCLC suggests that the role of prophylactic cranial irradiation in the management of early NSCLC should be explored. No significant financial relationships to disclose. [Table: see text]

Plasma Amino Acids in Experimental Acute Hepatic Failure and Their Relationship to Brain Tryptophan

1974 ◽  
Vol 46 (4) ◽  
pp. 559-562 ◽  
Author(s):  
B. H. Buxton ◽  
D. A. Stewart ◽  
I. M. Murray-Lyon ◽  
G. Curzon ◽  
R. Williams
Keyword(s):  
Amino Acids ◽  
Experimental Model ◽  
Hepatic Failure ◽  
Acute Hepatic Failure ◽  
Plasma Amino Acids ◽  
Neutral Amino Acids ◽  
Tryptophan Concentration ◽  
The Brain ◽  
Apparent Influence

1. Sixteen plasma amino acids were measured serially in an experimental model of acute hepatic failure produced in the pig by devascularization of the liver. 2. Significant increases in the concentration of glycine, alanine and methionine were observed. 3. Altered concentrations in plasma of neutral amino acids which compete with tryptophan for transport into the brain had no apparent influence on brain tryptophan concentration.

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