The entry into the brain of large molecules derived from dietary protein

1978 ◽  
Vol 200 (1139) ◽  
pp. 175-192 ◽  
Keyword(s):  
Specific Activity ◽  
Gel Filtration ◽  
Immune Serum ◽  
The Body ◽  
Brain Extract ◽  
Blood Contamination ◽  
Adult Rats ◽  
Large Molecules ◽  
Derivatives Of ◽  
The Brain

When bovine IgG, haemoglobin, or α-gliadin extracted from wheat, labelled with radio-iodine, are fed by stomach tube to suckling or adult rats, significant amounts of protein-bound radioactivity are found in extracts of whole brain. These amounts are greatly in excess of what can be accounted for by blood contamination: the specific activity of the brain is of the order of that of other tissues of the body, suggesting that it is permeated with protein derivatives of the fed material. This is borne out by differential centrifugation of brain macerates which shows sub­stantial protein-bound radioactivity in the cell sap fraction. Ultracentrifugation studies reveal the presence of high molecular mass material in the cell sap, some of greater sedimentation velocity than the original protein fed, suggesting complexing of derivatives of this with native components of the brain. This is confirmed by gel filtration studies. Immunological studies on the brain extract show that a high proportion of the protein-bound radioactivity of the brain retains the ability to be precipitated by specific immune serum, when α-gliadin or bovine IgG has been fed.

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.

Maternal dietary deficiency and its effect on the metabolism of nucleic acids and proteins. "Effect of exchanging the young, during the lactation period, between the control and undernourished female rats"

1978 ◽  
Vol 56 (2) ◽  
pp. 274-286 ◽  
Author(s):  
Tapas Goswami ◽  
Uma Srivastava
Keyword(s):  
Nucleic Acids ◽  
Protein Content ◽  
Specific Activity ◽  
The Body ◽  
Female Rats ◽  
Control Group ◽  
Lactation Period ◽  
Specific Activities ◽  
The Brain ◽  
Dietary Deficiency

The effect of maternal dietary deficiency on the metabolism of nucleic acids and proteins was studied by exchanging the pups of control and undernourished dams during the lactation period. In the pups of control dams fostered by undernourished dams during the lactation period (E3), it was observed that the body and organ weight, and RNA, DNA, and protein content failed to increase normally. Contrary to this, the free leucine and nucleotide contents were higher and their specific activities lower in the plasma and various organs of the E3 group as compared with the control group.Specific activity of protein was higher in the liver, brain, kidney, and lung, and was lower in the spleen and heart of the E3 group as compared with the control group. Specific activity of RNA was higher in the liver, spleen, and lung, and was lower in the brain, kidney, and heart of the E3 group as compared with the control group.In the pups of undernourished dams fostered by the control dams during the lactation period (E1), the body and organ weights, the RNA, DNA, and protein content, the content of free leucine and nucleotides as well as their specific activities, and the specific activity of protein and RNA were partially or completely restored. However, the DNA content of the brain remained unchanged in comparison with those pups of undernourished dams nursed by their own mother (E2). In the brain, kidney, spleen, and lung of the E1 group, the specific activity of RNA increased considerably and even exceeded the control values.The radioactivity results discussed above clearly demonstrate an accelerated metabolism of protein and RNA in the various organs of the E3 group and a partial or complete normalization in the E1 group.

scholarly journals A monoclonal antibody to bovine brain inositol monophosphatase. Immunoaffinity purification of the brain and kidney enzymes and evidence for their structural identity

1989 ◽  
Vol 264 (3) ◽  
pp. 793-798 ◽  
Author(s):  
N S Gee ◽  
S Howell ◽  
G Ryan ◽  
C I Ragan
Keyword(s):  
Monoclonal Antibody ◽  
Specific Activity ◽  
Binding Capacity ◽  
Bovine Brain ◽  
High Yield ◽  
Brain Extract ◽  
Kidney Cortex ◽  
Inositol Monophosphatase ◽  
Hydrolysis Of ◽  
The Brain

A monoclonal IgG2b(K) antibody, G-2A4, has been generated against bovine brain myo-inositol monophosphatase (EC 3.1.3.25). The identity of the antigen recognized by the antibody was established by using e.l.i.s.a. and Western blotting procedures, and by immunoprecipitation of enzyme activity from crude brain supernatant. In addition, the hydrolysis of Ins1P by crude brain extract was inhibited by up to 83% by the pure antibody. Under identical conditions, the hydrolysis of Ins(1,4)P2 was unaffected. An immunoadsorbent column containing monoclonal antibody G-2A4 covalently attached to CNBr-activated Sepharose 4B has been used for rapid purification of the brain enzyme. Elution conditions have been optimized to allow isolation of the enzyme in high yield (54%) with full retention of column-binding capacity. The enzyme was electrophoretically homogeneous, Mr 30,000 and of higher specific activity than that purified conventionally. Chromatography of the pure enzyme on high resolution ion-exchange columns revealed some charge heterogeneity, possibly indicative of some type of post-translational modification. The immunoadsorbent column has also been used to purify the bovine kidney cortex enzyme to homogeneity. Partial proteolytic fragmentation patterns of the brain and kidney enzymes using endoprotease glu-C were identical, suggesting that they are almost certainly products of the same gene.

scholarly journals The uptake of radioactive copper by the brain and other tissues of the developing rat

1970 ◽  
Vol 24 (3) ◽  
pp. 727-734 ◽  
Author(s):  
Deirdre Ryan ◽  
P. J. Warren
Keyword(s):  
Aqueous Solution ◽  
Initial Dose ◽  
Specific Activity ◽  
Copper Chloride ◽  
Age Groups ◽  
The Body ◽  
Steady Decrease ◽  
Liver And Kidney ◽  
Developing Rat ◽  
The Brain

1. 64Cu as copper chloride in aqueous solution was given by intraperitoneal injection to rats varying in age from a few hours to 14 weeks. The isotope was allowed to circulate in the body for 24 h.2. The amount of gamma radioactivity present in the brain and blood was measured and the percentage of the initial dose present was calculated. It was shown that the brain 64Cu activity reached a maximum around the 16th day of life and that the blood showed a steady decrease in the 64Cu activity per g from birth to maturity. Measurements were also made on the liver and kidney.3. The excretion of 64Cu in the urine and faeces in 24 h was also studied. Approximately 30% of the isotope was excreted in that time, mostly in the faeces.4. A limited number of experiments in three different age groups were carried out to discover whether changes in specific activity of the isotope given to rats had a significant effect on the percentage of 64Cu taken up by the brain and blood. No such effect was seen.

scholarly journals Evolution of phosphagen kinase1: Isolation, characterization and cDNA-derived amino acid sequence of two-domain arginine kinase from the sea anemone Anthopleura japonicus

1997 ◽  
Vol 328 (1) ◽  
pp. 301-306 ◽  
Author(s):  
Tomohiko SUZUKI ◽  
Yoshitada KAWASAKI ◽  
Takahiro FURUKOHRI
Keyword(s):  
Creatine Kinase ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Specific Activity ◽  
Arginine Kinase ◽  
Gel Filtration ◽  
Sea Anemone ◽  
The Body ◽  
Native Form ◽  
Significant Similarity

Arginine kinase (AK) was isolated from the body wall muscle of the primitive sea anemone Anthopleura japonicus by Ultrogel AcA34 gel filtration, DEAE-32 chromatography and elution on a Cosmogel-SP column. The denatured molecular mass as determined with SDS/PAGE was 80 kDa, twice that of the usual AK subunit, indicating that this AK has an unusual two-domain structure. The native form was eluted on a Superose 12 column with the same retention time as that of rabbit homodimeric creatine kinase, indicating that Anthopleura AK is a monomer of 80 kDa. The isolated enzyme gave a specific activity of 100-120 μmol of Pi/min per mg of protein in the pH range 7.9-9.1 for the forward reaction. The enzyme is fully activated by Ca2+, as it is with Mg2+. The cDNA-derived amino acid sequence of 715 residues of Anthopleura AK was determined. The validity of the sequence was supported by chemical sequencing of internal tryptic peptides. A bridge intron of 686 bp, which separates the two domains of Anthopleura AK, is present between the second and third nucleotide in the codon of Ala-364. This is the first two-domain AK to be sequenced. Anthopleura AK shows 48-54% amino acid sequence identity with known invertebrate AKs, and also shows a lower, but significant, similarity (39-46%) to marine worm glycocyamine kinase and rabbit creatine kinase.

RELEASE AND TRANSACYLATION OF ARACHIDONATE FROM A COMMON POOL OF 1-ACYL-2-ARACHIDONOYL GLYCEROPHOSPHOCHOLINE IN HUMAN PLATELETS

1987 ◽  
Author(s):  
A D Purdon ◽  
J B Smith
Keyword(s):  
Molecular Species ◽  
Specific Activity ◽  
Gel Filtration ◽  
Human Platelets ◽  
Time Interval ◽  
Resting Cells ◽  
Ether Phospholipid ◽  
Before And After ◽  
Layer Chromatography ◽  
Derivatives Of

We have previously shown that the main source of arachidonate in thrombin-stimulated human platelets is 1-acyl-2-arachidonoyl (AA) glycerophosphocholine (GPC) and release of 3H-AA from this phospholipid also was correlated with increased 3H-AA in ether phospholipid. This ATP independent transfer of 3H-AA from 1,2 diacyl GPC to ether phospholipid (transacylation) also occurs in resting cells. Human platelets in 1/10 volume of plasma (ACD anticoagulant, pH 6.5) were radiolabelled with 3H-AA for 60 min at 37°C and then exogenous 3H-AA was removed by gel filtration into Tyrode's buffer, pH 7.4, 0.2% albumin. These radiolabelled cells were incubated in the absence of exogenous 3H-AA for four hours followed by Bligh and Dyer extraction and thin layer chromatography purification of phospholipids. 3H-AA in 1,2 diacyl GPC was found to decrease by over 20% and increase substantially in 1-0-alkyl-2-acyl GPC and 1-0-alk-1'-enyl-2-acyl glycerophospho ethanolamine (GPE), In this same time interval the mass of AA released by thrombin (5 U/ml, 10 min, 37°C, no stirring)in the presence of BIT 775C and measured by GLC, stayed the same (30 nmoles/109 cells), however, the specific activity decreased. Using reverse phase HPLC to resolve diradylglycerobenzoate derivatives of phospholipids: acylation, deacylation, and transacylation were observed for individual AA-containing molecular species of phospholipid, including those with an unsaturated fatty acid at sn-1. In particular the radiolabellinq of the 1-unsaturate-2-arachidonoyl GPC correlated with the specific activity of the 3H-AA released by stimulation with thrombin. Furthermore, 1-arachidonoyl-2-3H-arachidonoyl GPC was completely deacylated while 50 % of its mass remained. This contrasted with 16:0, and 18:0-2-arachidonoyl GPC in which the specific activity remained the same before and after deacylation. We conclude that deacylation of AA-containing molecular species of 1,2 diacyl GPC in stimulated cells includes molecular species which are also a source of arachidonic acid for transacylation reactions.

scholarly journals The phosphorus metabolism of the brain

1950 ◽  
Vol 137 (887) ◽  
pp. 252-267 ◽  
Keyword(s):  
Specific Activity ◽  
Specific Effect ◽  
Phospholipid Metabolism ◽  
The Body ◽  
Sodium Pentobarbital ◽  
Rotating Drum ◽  
Radioactive Phosphorus ◽  
Phosphorus Containing ◽  
The Brain

The metabolism of the brain in vivo has been studied by measuring the rate of uptake of radioactive phosphorus into the different phosphorus-containing fractions of the mouse brain. By the use of specific-activity ratios referred to the acid-soluble fraction of the brain, satisfactorily constant values were obtained for the uptake into the nucleoprotein and phospholipid fractions in normal animals. The observed ratios indicated a relatively high metabolic activity for these fractions under normal conditions in vivo . The uptake of radioactive phosphorus into the nucleoprotein and phospholipid fractions of the brain was decreased in sodium pentobarbital anaesthesia; the effect was greater if the body temperature was also allowed to fall. Electrically induced convulsions and insulin hypoglycaemia caused a significant decrease in the uptake of radioactive phosphorus into the brain phospholipids without a corresponding change in the nucleoprotein fraction. A similar specific effect on the phospholipid metabolism was observed under normal physiological conditions in animals exposed for 3 hr. in a rotating drum. The effect was absent in animals which had previously been conditioned to the rotating drum. The results give evidence that the metabolism of the permanent or ‘structural’ elements of nervous tissue, as well as of the more labile metabolites, may vary in vivo with the state of functional activity of the brain.

EXPERIMENTAL ASSESSMENT OF THE NANOPARTICLES TOXICITY OF NICKEL OXIDE IN TWO SIZES IN THE SUBCHRONIC EXPERIMENT

2018 ◽  
pp. 30-35
Author(s):  
M.P. Sutunkova ◽  
B.A. Katsnelson ◽  
L.I. Privalova ◽  
S.N. Solovjeva ◽  
V.B. Gurvich ◽  
...  
Keyword(s):  
Nickel Oxide ◽  
Nervous Activity ◽  
Equal Mass ◽  
The Body ◽  
Subchronic Toxicity ◽  
Physiological Mechanisms ◽  
Nickel Oxide Nanoparticles ◽  
The Relationship ◽  
The Brain ◽  
Nanoparticles Toxicity

We conducted a comparative assessment of the nickel oxide nanoparticles toxicity (NiO) of two sizes (11 and 25 nm) according to a number of indicators of the body state after repeated intraperitoneal injections of these particles suspensions. At equal mass doses, NiO nanoparticles have been found to cause various manifestations of systemic subchronic toxicity with a particularly pronounced effect on liver, kidney function, the body’s antioxidant system, lipid metabolism, white and red blood, redox metabolism, spleen damage, and some disorders of nervous activity allegedly related to the possibility of nickel penetration into the brain from the blood. The relationship between the diameter and toxicity of particles is ambiguous, which may be due to differences in toxicokinetics, which is controlled by both physiological mechanisms and direct penetration of nanoparticles through biological barriers and, finally, unequal solubility.

Synthesis and Antimicrobial Activity of Adamantyl Substituted Pyridoxine Derivatives

2019 ◽  
Vol 16 (12) ◽  
pp. 1360-1369 ◽  
Author(s):  
Rail Khaziev ◽  
Nikita Shtyrlin ◽  
Roman Pavelyev ◽  
Raushan Nigmatullin ◽  
Raylya Gabbasova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Lipid Membranes ◽  
Specific Activity ◽  
Tuberculosis H37rv ◽  
Microbial Pathogens ◽  
Adamantane Derivatives ◽  
Carbon Cage ◽  
H37rv Strain ◽  
Derivatives Of

Background: Adamantane derivatives possess multiple pharmacological activities such as antiviral, anticancer, antimycobacterial, antidiabetic, antiparkinsonian and others. The interest of medicinal chemists in adamantane compounds is due to their unique spatial structure, high lipophilicity, and carbon cage rigidity. As a result, these molecules can easily penetrate biological lipid membranes and often have unique target-specific activity profile. Another pharmacophore studied in this work is pyridoxine (vitamin B6). Pyridoxine plays highly important roles in living cells as a key cofactor of many enzymes. On the other hand, its molecular scaffold is a valuable structural platform which has led to the development of several launched drugs (Pyritinol, Pirisudanol, Cycletanine, Mangafodipir) and a wide number of preclinical and clinical drug candidates. Objective: The objective of this study is a synthesis of pyridoxine-adamantane and pyridoxinecyclooctane dipharmacophore molecules. The underlying idea was to assess the antibacterial and antiviral potential of such dipharmacophores, based on multiple examples of promising antiinfective agents which have in their structures adamantane and pyridoxine moieties. Another specific reason was to explore the ability of pyridoxine pharmacophore to suppress the potential of microbial pathogens to develop resistance to drug molecules. Methods: In this study, a series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkyl amines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. All synthesized compounds have been tested for their in vitro activity against M. tuberculosis H37Rv strain and H3N2 (A/Aichi/2/68) influenza virus. Results: Series of pyridoxine-adamantane and pyridoxine-cyclooctane dipharmacophore molecules were synthesized based on reactions of three different cycloalkylamines with the corresponding electrophilic derivatives of pyridoxine aldehydes, chlorides and acetates. Reaction of cycloalkylamines with pyridoxine derivatives, in which meta-hydroxyl and ortho-hydroxymethyl groups are protected by acetyl groups, represents a useful alternative to reductive amination of aldehydes and nucleophilic substitution of alkyl halides. According to a tentative mechanism, it proceeds via paraand ortho-pyridinone methides which readily react with nucleophiles. None of the synthesized dipharmacophore compounds showed activity against M. tuberculosis H37Rv strain. At the same time, three compounds demonstrated some antiviral activity against H3N2 (A/Aichi/2/68) influenza virus (EC50 52-88 µg/mL) that was comparable to the activity of Amantadine, though lower than the activity of Rimantadine. The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane. Conclusion: The results of this work can be useful in the design of physiologically active derivatives of pyridoxine and adamantane.

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