bluuebunny/crossref_metadata_2025_split huggingface dataset:
An open label randomized comparison of mefloquine–artesunate as separate tablets vs. a new co‐formulated combination for the treatment of uncomplicated multidrug‐resistant falciparum malaria in Thailand
Authors: Ashley Elizabeth A. , Lwin Khin Maung , McGready Rose , Simon Win Htay , Phaiphun Lucy , Proux Stephane , Wangseang Nantawan , Taylor Walter , Stepniewska Kasia , Nawamaneerat Wimon , Thwai Kyaw Lay , Barends Marion , Leowattana Wattana , Olliaro Piero , Singhasivanon Pratap , White Nicholas J. , Nosten François 
Published: October 2006

SummaryBackground  Delivering drugs in a fixed combination is essential to the success of the strategy of artemisinin‐based combination therapy. This prevents one drug being taken without the protection of the other, reducing the chance of emergence and spread of drug resistant strains of Plasmodium falciparum. A lower tablet burden should also facilitate adherence to treatment. A new fixed combination of mefloquine plus artesunate has been developed. This was compared with the conventional regimen of separate tablets for the treatment of uncomplicated multidrug‐resistant falciparum malaria.Methods  On the north‐western border of Thailand 500 adults and children with uncomplicated falciparum malaria were randomized to receive either the new fixed combination or separate tablets. They were followed up weekly for 63 days.Results  The day 63 polymerase chain reaction‐adjusted cure rates were 91.9% (95% CI 88.2–95.6) in the fixed combination group and 89.2% (85.0–93.4) in the loose tablets group (P = 0.3). There was a lower incidence of early vomiting in the group receiving the fixed combination.Conclusion  This new fixed combination of mefloquine and artesunate was efficacious, well tolerated and convenient to administer.Keywords  artemisinin , fixed combination , malaria , mefloquine
REGIONAL DISTRIBUTION OF γ‐AMINOBUTYRIC ACID (GABA) IN BRAIN OF THE RHESUS MONKEY*
Authors: Fahn S. , Ccote L. J. 
Published: October 2006

Abstract—The concentrations of γ‐aminobutyric acid (GABA) in twenty different regions of Rhesus monkey brain were studied. The highest levels were found in the substantia nigra, globus pallidus, and hypothalamus. Regions of the cerebral cortex and thalamus contained low amounts and white matter the lowest. Indirect evidence supporting an inhibitory transmitter role for GABA is discussed.
LOCALIZATION OF γ‐AMINOBUTYRIC‐α‐OXOGLUTARIC ACID TRANSAMINASE IN MOUSE BRAIN*
Authors: Waksman A. , Rubinstein M. K. , Kuriyama K. , Roberts E. 
Published: October 2006

AbstractThe distribution of γ‐aminobutyric‐α‐oxoglutarate transaminase (GABA‐T) has been studied in mouse brain by histochemical visualization on sections, quantitative determination in grossly dissected brain regions, and in subcellular fractions prepared from whole brain homogenates. The results indicate that GABA‐T is predominantly a mitochondrial enzyme and that its concentration is particularly high in brain stem areas. The results are discussed in relation to the overall function of the GABA system in the CNS.
TETANUS TOXIN AND AMINO ACID LEVELS IN CAT SPINAL CORD
Authors: Johnston G. A. R. , de Groat W. C. , Curtis D. R. 
Published: October 2006

Abstract— —The levels of the depressant amino acids found in appreciable amounts in cord extracts—α‐alanine, cystathionine, GABA, glycine and serine—were not significantly influenced by tetanus toxin. This supports the view that the antagonism of spinal inhibition by the toxin is the result of an interference with transmitter release rather than a reduction in the amount of transmitter available for release.The marked increase in aspartic acid levels found in the spinal cord after treatment with tetanus toxin may reflect the association of aspartic acid with the increased activity of spinal excitatory interneurones or the involvement of aspartic acid as a glycine precursor in spinal tissue.
A STUDY OF LIPID COMPONENTS IN BRAIN OF THE ‘JIMPY’ MOUSE, A MUTANT WITH MYELIN DEFICIENCY
Authors: Nussbaum J. L. , Neskovic N. , Mandel P. 
Published: October 2006

Abstract—(1) Brain composition and developmental changes were investigated in a mutant (‘Jimpy’) mouse characterized by a severe myelin deficiency.(2) Significantly lower cholesterol, phospholipid and galactolipid values were observed, and the accumulation of these lipids during the myelination period was markedly reduced or absent.(3) The most remarkable feature of ‘Jimpy’ brain was a very small galactolipid content. In 29‐day‐old mutants the concentration of galactolipids was 0‐18 μ moles/g wet wt., representing a 46‐fold decrease when compared to values determined in normal mice.(4) There was no such striking change in the distribution of different phospholipids. However, lowered relative amounts of some phospholipids, e.g. ethanolamine plasmalogen, sphingomyelin and phosphatidylserine, were observed in ‘Jimpy’ brain.(5) Protein content was also lower in mutant brains and showed an absolute decrease after 23 days of life.(6) These data support the statement that the process of myelination is disturbed at an early stage, resulting in a deficiency of mature myelin sheaths and leading probably to the breakdown of primitive myelin structures.
METABOLISM OF GLUCOSE AND REDUCTION OF RETINALDEHYDE IN RETINAL PHOTORECEPTORS1
Authors: Futterman S. , Hendrickson Anita , Bishop P. E. , Rollins Martha H. , Vacano Elsi 
Published: October 2006

Abstract—The capacity of a variety of substrates to support reduction of retinaldehyde to retinol by preparations of outer segments from photoreceptor cells of bovine retina, the requirement for supplements, the effect of iodoacetate, and the stoichiometry of the metabolism of glucose and the reduction of retinaldehyde have been studied. Metabolism of glucose supported reduction of retinaldehyde by preparations of outer segments at approximately the rate observed for the intact retina. Throughout the physiological range of pH, the dehydrogenase reactions of the pentose cycle in outer segments provided virtually all of the reduced pyridine nucleotides that were utilized for reduction of retinaldehyde. It was concluded that reduction of retinaldehyde during light adaptation is exclusively dependent upon NADPH.
ON THE ORIGIN OF THE ACETYL MOIETY OF ACETYLCHOLINE IN BRAIN STUDIED WITH A DIFFERENTIAL LABELLING TECHNIQUE USING 3H‐14C‐MIXED LABELLED GLUCOSE AND ACETATE
Authors: Sollenberg J. , Sörbo B. 
Published: October 2006

Abstract—Cortex slices of rat brain were incubated with glucose mixed‐labelled with 3H and 14C in the 6‐position and the 3H/14C ratios of lactate, acetate, citrate and acetylcholine were determined. The values obtained were: lactate 0·95, acetate 0·85, citrate 0·65 and acetylcholine 0·67 when expressed in relation to a glucose 3H/14C ratio of 1·00. When brain slices were incubated with [2‐14C, 2‐3H]acetate in the presence of unlabelled glucose, labelled acetylcholine was formed with a 3H/14C ratio not significantly different from the labelled substrate. The results indicate that citrate is a precursor to the acetyl moiety of acetylcholine.
LEVELS OF MYO‐INOSITOL IN NORMAL AND DEGENERATING PERIPHERAL NERVE1
Authors: Kusama H. , Stewart M. A. 
Published: October 2006

Abstract—Free inositol was measured in peripheral nerves of the monkey, rabbit, rat, frog and lobster; levels in mammalian nerve were similar, and two to three times greater than in the other species. Concentrations of myo‐inositol in rabbit tibial nerve increased from proximal to distal segments; in optic nerve the concentrations decreased with greater distance from the retina. In the early stages of Wallerian degeneration rabbit tibial nerve contained 25 per cent less free myo‐inositol, rat nerve 50 per cent less. Rabbit nerves were analysed at 2 and 5 weeks after section; by 5 weeks levels of myo‐inositol had increased to 50 per cent above normal. Similar changes were found in degenerating rabbit optic nerve. The combination of galactose feeding and nerve section resulted in reduction of the myo‐inositol in rat sciatic nerve to one‐fifth of the control value; galactitol in the nerve decreased by 50 per cent after section. The evidence suggests that myo‐inositol in nerve is located mainly in Schwann cells or glia.
BASE‐EXCHANGE REACTIONS FOR THE SYNTHESIS OF PHOSPHOLIPIDS IN NERVOUS TISSUE: THE INCORPORATION OF SERINE AND ETHANOLAMINE INTO THE PHOSPHOLIPIDS OF ISOLATED BRAIN MICROSOMES1,2
Authors: Porcellati G. , Arienti G. , Pirotta M. , Giorgini D. 
Published: October 2006

Abstract— The calcium‐dependent incorporation of l‐[3‐3H]serine and [1,2‐14C]ethanol‐amine into the phospholipid of isolated subcellular fractions from chick brain was studied and the properties of incorporation were examined. The microsomal fraction was found to possess the highest rate of incorporation and was able to convert under optimal conditions about 120 nmol of labelled serine and 220 nmol of ethanolamine/g of fresh brain microsomes/h. The requirement for Ca2+ ion appeared to be absolute. Mg2+ ion caused a gradual reduction in the existing enzymic activity, only when pre‐incubated with microsomes and labelled bases before adding Ca2+ ion. The incorporation of serine and ethanolamine was actively inhibited by Hg2+, Co2+, Cu2+ and Mn2+ ions, and was abolished by ethylenediamine tetra‐acetate treatment. Ethanolamine, but not choline, inositol or carnitine, competitively inhibited serine incorporation, while d‐serine had slight effect. Conversely, l‐serine inhibited competitively the incorporation of ethanolamine.The greater part of the incorporated serine (85 per cent) was localized in microsomal phosphatidylserine, while a small percentage was found in phosphatidylethanolamine. Similarly, 90 per cent of the incorporated ethanolamine was confined to phosphatidylethanolamine and a small percentage was found in the plasmalogen derivative. The mechanism of serine and ethanolamine incorporation was investigated. The results are compared with those published for similar mammalian and non‐mammalian systems.
CHARACTERISTICS OF AMINO ACID ACCUMULATION BY SYNAPTOSOMAL PARTICLES ISOLATED FROM RAT BRAIN
Authors: Peterson N. A. , Raghupathy E. 
Published: October 2006

Abstract—The characteristics of the accumulation of 14 L‐amino acids (Leu, Ileu, Val, His, Tyr, Phe, Gly, Ala, Ser, Thr, Asp, Pro, Arg and Lys) by synaptosomal fractions prepared from rat brains were studied. Distinct differences were observed in the ion requirements for the accumulation of these amino acids. The accumulation of Asp and Pro alone showed a total requirement for Na+; uptakes of the other amino acids were either maximal in Na+‐free media or only partially dependent on the presence of external Na+. With brain maturation, two types of developmental alterations could be distinguished: (1) changes in rates of influx, and (2) changes in the effects of ions. Synaptosomal fractions prepared from brains of immature rats accumulated Leu, Arg and Lys to a greater extent and Val, Tyr, Pro and Asp to a lesser extent than did the fractions prepared from brains of mature animals. The accumulation of Ser and Thr by immature fractions was partially dependent on external Na+, whereas their accumulation by adult fractions was Na+‐independent. These alterations in Na+ requirements coincided with developmental changes in mutual inhibitions of amino acid transport.
ZINC IN MATURING RAT BRAIN: HIPPOCAMPAL CONCENTRATION AND LOCALIZATION1
Authors: Crawford I. L. , Connor J. D. 
Published: October 2006

Abstract—Alterations in the localization and concentration of zinc in the hippocampus and in other regions of rat brain were studied during postnatal maturation. Histochemical observations indicated increasing levels of zinc in the hippocampal mossy fibre layer at about 20 days of age. Between 18 and 22 days, hippocampal levels of zinc increased by 35 per cent to reach adult levels (121 ng/mg of protein). After subcellular fractionation, more than one‐half of the hippocampal zinc was found in the first pellet (P1; 1085 g– 10 min), where large boutons would be expected. Autoradiographic evidence, revealing the sequential location of positron tracks first in the granular cell layer and later in the mossy fibre layer, raises the possibility of axoplasmic transport of zinc from granule cell perikarya to their terminal boutons. Our data suggest that zinc may be involved in the maturation and function of the mossy fibre pathway.
PATTERNS OF AMINO ACID RELEASE FROM NERVE‐ENDINGS ISOLATED FROM SPINAL CORD AND MEDULLA
Authors: Osborne R. H. , Bradford H. F. , Jones D. G. 
Published: October 2006

AbstractThe metabolic properties of synaptosomes prepared from the crude mitochondrial and crude nuclear fractions of the medulla/spinal cord were studied. They showed similar properties, glycine being enriched in the latter. The respiration and glycolysis rates were similar to the cortical synaptosomes previously studied. A major difference from cortical synaptosomes was the enrichment of glycine. Medulla/spinal cord synaptosome suspensions and beds responded metabolically to electrical pulses; respiration and lactate production increased by 50 and 25 per cent respectively. Differential release of glutamate, aspartate, GABA and glycine occurred during both electrical stimulation, and when potassium in the medium was increased. Omitting calcium and adding EGTA greatly reduced this response with both forms of stimulation. The electrically induced release of GABA was completely reversible whilst that of aspartate and glycine was only partially reversible. The electrically stimulated release of glycine and other amino acids was reduced in synaptosomes prepared from rats treated intramuscularly with tetanus toxin 15 hr before death. No action of the toxin was seen on synaptosomes incubated with tetanus toxin after preparation.
ENZYMIC AND CEREBRAL METABOLIC EFFECTS OF 2‐DEOXY‐d‐GLUCOSE
Authors: Horton R. W. , Meldrum B. S. , Bachelard H. S. 
Published: October 2006

Abstract—The time course of effects of 2‐deoxy‐d‐glucose on cerebral glucose metabolism has been studied in vivo and the inhibitory actions of 2‐deoxy‐d‐glucose and 2‐deoxy‐d‐glucose‐6‐phosphate on cerebral glycolytic enzymes in vitro. Mice were given 2‐deoxy‐d‐glucose 3 g/kg intraperitoneally. Blood 2‐deoxy‐d‐glucose/glucose ratio was 2–3 from 5 to 30 min after injection, the hyperglycaemic response to 2‐deoxy‐d‐glucose having been suppressed with propranolol. Maximal cerebral 2‐deoxy‐d‐glucose uptake observed was 1μ11 μmol/g/min between 5 and 10 min after injection. At 10 min brain concentrations of 2‐deoxy‐d‐glucose and 2‐deoxy‐d‐glucose‐6‐phosphate were 5·82 and 3·12 μmol/g. Analysis of the fate of d‐[U‐14C] glucose given subcutaneously 5 min before death showed that glucose uptake was reduced to 40–60 per cent of control from 5 to 30 min after 2‐deoxy‐d‐glucose. However brain glucose concentration rose three to five‐fold 20–30 min after 2‐deoxy‐d‐glucose. The majority of glucose entering the brain after 10 min of 2‐deoxy‐d‐glucose treatment was recovered as glucose. Conversion of brain glucose to other acid soluble components was reduced to 1/3 at 10 min and 1/5 at 20–30 min. Glucose‐6‐phosphate concentration rose from 5 min onwards and was maintained at twice control concentration from 10–30 min. However, because of the rapid entry of 2‐deoxy‐d‐glucose and its conversion to 2‐deoxy‐d‐glucose‐6‐phosphate, the 2‐deoxy‐d‐glucose 6‐P/glucose 6‐P ratio was between 19 and 32. Brain adenosine triphosphate concentration did not change, creatine phosphate concentration fell after 25 min.Measurement of enzyme activities in cerebral homogenates (using 1 mivs substrate concentration) showed that hexokinase (EC 2.7.1.1) was 40 per cent inhibited by 5 mm‐deoxy‐d‐glucose (but not by 2‐deoxy‐d‐glucose 6‐P). Glucose 6‐P dehydrogenase (EC 1.1.1.49), 6‐phosphogluconate dehydrogenase (EC 1.1.1.43) and phosphoglucomutase (EC 2.7.5.1) were not affected by either 2‐deoxy‐d‐glucose (5 mm) or 2‐deoxy‐d‐glucose 6‐P (5 or 20 mm). Hexose‐phosphate isomerase (EC 5.3.1.9) was 70 per cent inhibited by 20 mm‐d‐deoxy‐d‐glucose 6‐P. Phosphofructokinase (EC 2.7.1.11) was inhibited by 17 per cent by 2‐deoxy‐d‐glucose 6‐P (20 mm). During the initial impairment of cerebral function by 2‐deoxy‐d‐glucose there is competitive inhibition of glucose transport into the brain; later, glycolysis is more powerfully depressed by the inhibition of isomerase produced by the high intracerebral concentration of 2‐deoxyglucose‐6‐phosphate.
DEVELOPMENT OF Na+‐STIMULATED GLUCOSE OXIDATION IN SYNAPTOSOMES1,2
Authors: Diamond I. , Fishman R. A. 
Published: October 2006

Abstract— d‐[14C]Glucose was oxidized to 14CO2 by synaptosomes prepared from adult rat brain. Added Na+ stimulated glucose oxidation by 179%, but K+ and choline were without effect. Li+ stimulated glucose oxidation by 64%. Ouabain largely prevented the stimulatory effect of Na+ on glucose oxidation but had no effect in the absence of Na+. 2‐Deoxy‐d‐glucose competitively inhibited glucose oxidation differently at two different ranges of deoxyglucose and glucose concentrations; the Ki was 0.54 and 16 mm, respectively. In the presence or absence of Na+ 2,4‐DNP‐stimulated glucose oxidation by 370% while iodoacetate inhibited glucose oxidation by 87–95%. There was a striking increase in Na+‐stimulated glucose oxidation with development but glucose oxidation in the absence of Na+ did not change dramatically with age.Taken together the data suggest synaptosomes exhibit coupled respiration which can be modulated by Na+. In addition, the appearance of Na+‐stimulated glucose oxidation with maturation probably is linked to the development of Na+‐K+‐ATPase acitivity in the synaptosomal membrane.
UPTAKE AND RELEASE OF [14C]ADENINE DERIVATIVES AT BEDS OF MAMMALIAN CORTICAL SYNAPTOSOMES IN A SUPERFUSION SYSTEM
Authors: Kuroda Y. , McIlwain H. 
Published: October 2006

Abstract(1) Synaptosomal fractions from guinea pig neocortical dispersions prepared in sucrose solutions were deposited from saline media as ‘beds’ on nylon bolting cloth. When incubated with 0.5–10 μm‐[14C]adenine or adenosine in glucose bicarbonate salines, uptake of 14C from adenosine proceeded at about four times the rate of uptake of [14C]adenine. This contrasted with the relative uptake of the two compounds to neocortical tissue slices or to beds made from mitochondrial fractions, where uptake was similar with the two precursors. Uptake of both precursors to synaptosome beds was much greater than uptake of inosine.(2) Synaptosome beds, [14C]adenosine‐loaded, contained 88 per cent of the 14C as 5′‐adenine nucleotides, the remainder being present as cyclic AMP, inosine, hypoxanthine and adenosine. When superfused, the 14C output consisted mainly of adenosine, inosine and hypoxanthine, with some 7 per cent of 5′‐nucleotides and 4 per cent of cyclic AMP.(3) Electrical pulses and the addition of 50 mm‐KCl each increased the efflux of 14C from superfused [14C]adenosine‐loaded beds. The superfusates issuing after excitation contained the same 14C‐labelled compounds as issued before, with a small increase in the proportional yield of adenosine. The additional output of 14C following electrical pulses was diminished by about 50 per cent by 0.5 μm‐tetrodotoxin while that following KCl was not affected; it was however prevented when the superfusing fluids were free of Ca2+.
DISTRIBUTION OF SERINE HYDROXYMETHYLTRANSFERASE AND GLYCINE TRANSAMINASE IN SEVERAL AREAS OF THE CENTRAL NERVOUS SYSTEM OF THE RAT
Authors: Daly E. C. , Aprison M. H. 
Published: October 2006

Abstract—The regional distributions of serine hydroxymethyltransferase (SHMT) and glycine transaminase (GT) have been determined in five areas of the CNS of the rat. The SHMT activity per mg protein varied in these areas in the following order: medulia‐pons and spinal cord > cerebellum > midbrain > telencephalon. The GT activity per mg protein was essentially the same in the four brain areas, whereas, in the spinal cord it was lower. The activity of GT did not correlate with the glycine content (r=−0.45. P > 0.05). However, SHMT activity per mg protein was correlated with the glycine content in four regions (the telencephalon, midbrain, medulla‐pons and spinal cord; r= 0.997, P < 0.05). When the activity of SHMT was expressed per relative number of mitochondria, the enzyme levels were correlated with the glycine content in all five areas (r= 0.952, P < 0.05). The distribution of SHMT was determined in the primary subcellular fractions of the CNS. The SHMT activity in these areas of the CNS appeared to be located predominately in paniculate structures, while only 1 to 4 per cent was found in the soluble fraction. The crude nuclear (P1) and the crude mitochondrial (P2) fractions contained 90–97 per cent of the activity. Subfractionation of P2 pellets obtained from the telencephalon, medulla‐pons and spinal cord indicated the SHMT activity was localized in both ‘free’ and occluded mitochondria.
DISTRIBUTION OF GAMMA‐AMINOBUTYRIC ACID (GABA) IN THE RAT HYPOTHALAMUS: FUNCTIONAL CORRELATES OF GABA WITH ACTIVITIES OF APPETITE CONTROLLING MECHANISMS
Authors: Kimura H. , Kuriyama K. 
Published: October 2006

Abstract—In the hypothalamus, the highest GABA content (approx. 26 nmol/mm3) was constantly observed in the lateral hypothalamic area (LHA). In other parts of the hypothalamus uneven distribution of GABA was also observed, but areas showing high concentration of GABA did not coincide with the locations of various hypothalamic nuclei. In the LHA, which is known to contain a feeding centre, the anterior part (6.4 and 6.0 mm anterior (A 6.4 and A 6.0) respectively to the vertical zero plane of de Groot) showed a remarkably high content of GABA. The GABA content in the LHA at A 6.4 was decreased during the initial phase of insulin hypoglycemia and, in contrast, showed a significant increase following hyperglycemia induced by alloxan administration. In the ventromedial nucleus (VMH) of the hypothalamus, which is known to contain a satiety centre, the GABA content was increased during the initial phase of insulin hypoglycemia.The results suggest that both certain parts of the LHA and VMH contain or receive GABA‐inhibitory neurons and that these neurons may play important physiological roles in controlling functional states of the feeding and satiety centres in the hypothalamus.
INHIBITION OF THE TRANSPORT OF 5‐HYDROXYINDOLEACETIC ACID FROM BRAIN BY ETHANOL1
Authors: Tabakoff B. , Ritzmann R. F. , Boggan W. O. 
Published: October 2006

Abstract—The injection of ethanol in mice produced a transient rise in 5‐hydroxyindoleacetic acid (5‐HIAA) levels in brain. However, no concomitant changes in serotonin (5‐HT) levels were noted. In an attempt to explain the biochemical mechanism by which ethanol produced this effect, uptake of tryptophan by brain, serotonin turnover in brain, and transport of 5‐HIAA from brain were investigated. No changes in tryptophan levels or uptake into brain of ethanol‐treated mice were noted. Ethanol 3 g/kg was found to decrease serotonin turnover. Ethanol was also demonstrated to inhibit the removal of 5‐HIAA from the central nervous system, and was found to be an inhibitor of 5‐HIAA uptake by isolated choroid plexus. The inhibition of biogenic acid transport was noted even at sub‐hypnotic levels of ethanol.
INSULIN AND THE WAY THE BRAIN HANDLES GLUCOSE1
Authors: Daniel P. M. , Love E. R. , Pratt O. E. 
Published: October 2006

Abstract—In living rats the concentration of insulin in the circulating blood was raised and independently of this the glucose concentration in the blood plasma was varied from hyperglycaemic to hypoglycaemic levels. Hyperglycaemia increased the influx of glucose into the brain and it also, for a limited period, increased the glucose gain by the brain. Insulin, on the other hand, did not affect influx but significantly increased the gain of glucose by the brain. It is suggested that although both hyperglycaemia and insulin can increase glucose gain by the brain they do so in entirely different ways.