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P Brust

Publications and source records attributed to P Brust.

16 recordsLinked to original sources
PubMed1992

Density of perfused capillaries in living human brain during functional activation.

Recent evidence has indicated that functional activation of cerebral cortex is accompanied by increases of blood flow and glucose consumption but not oxygen consumption. No explanation has been advanced for this change of the flow-metabolism couple. We formulated the hypothesis that oxygen delivery to brain tissue is diffusion-limited by the enormous hemoglobin binding, and rate-limiting for the oxygen consumption of the tissue. One prediction of this hypothesis is very low oxygen tensions in the tissue. A second prediction is the inability of oxygen consumption to increase during functional activation in the absence of recruitment of capillaries for the oxygen diffusion capacity. We designed a study to test the latter prediction by calculating the density of functioning capillaries during vibrotactile stimulation of the parietal cortex. We defined functioning capillaries as capillaries that transport glucose and therefore calculated the capillary density from the glucose diffusion capacity (K1) of the cerebral capillaries. We confirmed the presence of a partial flow-CMRglc couple (2:1) during the functional activation. Oxygen consumption did not change despite an increase of capillary density in proportion to the change of blood flow.

Brain↗
PubMed1992

Effects of vasopressin on blood-brain transfer of methionine in dogs.

We used a simplified probe detection system for positron-emitting radionuclides in order to measure blood-brain barrier transport of amino acids in anesthetized dogs. Plasma and brain time-activity curves were recorded after intravenous bolus injection of L-[11C]methionine before and after administration of 1 microgram of vasopressin. Three-compartment models with three or four transfer coefficients were used to derive the kinetics of L-[11C]methionine uptake in brain. The blood-brain clearance of the tracer (K1) was 0.075 ml ml-1 min-1 before and 0.041 ml ml-1 min-1 after injection of vasopressin. The partition volume and the initial distribution (plasma) volume of methionine were unchanged and within the expected limits. The net accumulation rate of methionine (K), estimated by both the four-parameter (kinetic) and three-parameter (graphic) approaches, decreased after vasopressin injection in all six studies.

Animals↗
PubMed1992

Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin.

The extracellular amino acid concentrations in the left and right dorsal hippocampus of male rats were studied before and during application of vasopressin into the right hippocampus. The method of intracerebral microdialysis was used for both arginine vasopressin administration and monitoring of the composition of the extracellular fluid. The concentrations of 16 amino acids were measured by HPLC in the perfusate samples. The level of taurine declined 20% in the right hippocampus during perfusion with vasopressin, whereas o-phosphoethanolamine decreased in both sides, the left 20% and the right 24%. These alterations may be related to cerebral osmoregulation. Also, the levels of tyrosine and phenylalanine increased 15% and 35%, respectively, during administration of vasopressin. No changes of other amino acids were observed.

Amino Acids↗
PubMed1992

Changes in the blood-brain transfer of L-phenylalanine elicited by arginine vasopressin.

Arginine vasopressin (AVP) coinjected into the carotid artery in physiological concentrations (0.1 nmol/l) with L-[3H]phenylalanine changed the kinetic parameters of blood-brain barrier (BBB) transport of this neutral amino acid. The half-saturation constant (Km) and the maximum velocity of transport (Vmax) were estimated in nine brain regions of male Wistar rats anaesthetized with ether. In the cerebral hemisphere Km decreased significantly from 0.107 to 0.061 mmol/l and Vmax from 37.6 to 27.4 mmol/min/g. Comparing the kinetic constants for the phenylalanine transfer of corresponding regions of control animals and those coinjected with the amino acid and AVP, 8 out of 9 (Km) and 7 out of 9 (Vmax) regions were found significantly lowered. The findings support the hypothesis that AVP binding to the endothelial cell layer of the brain capillaries induces alterations of the transfer of at least the large neutral amino acids (LNAAs) from blood to brain. The kinetic parameters estimated for L-phenylalanine favour the assumption that in vivo AVP induces a preferred transport of this amino acid across the BBB compared to L-leucine.

Animals↗
PubMed1992

Effects of the nootropic AWD 52-39 on the blood-brain transfer of leucine, choline and glucose in rats after 14-d exposure to ethanol.

The transport of the neutral amino acid L-leucine as well as of choline and D-glucose across the blood-brain barrier (BBB) of male Wistar rats was studied after 14-day exposure to ethanol and treatment with the nootropic drug AWD 52-39 (1). After ethanol exposure the half-saturation constant (Km) and the maximum velocity of transport (Vmax) declined in the majority of the investigated brain regions. Also, the treatment elicited a regionally different increase of the permeability-surface area (PS) product of choline (between 10% and 33%) and glucose (between 12% and 27%). The changes in the blood-brain transfer of the three compounds were diminished or prevented by additional application of 1. The cerebral blood flow was increased by the exposure to ethanol by maximally 44%. After additional administration of 1 the changes were reversed and the blood flow reached control values. In addition, the activity of the enzyme acetylcholine esterase was determined in the striatum and the hippocampus. After ethanol exposure the enzyme activity declined by 32%. It was less diminished after treatment with 1. The latter effects let assume that the changes of the BBB permeability elicited by ethanol and 1 are related to alterations of brain metabolism.

Acetylcholinesterase↗
PubMed1992

On the blood-brain barrier to peptides: effects of immobilization stress on regional blood supply and accumulation of labelled peptides in the rat brain.

Tritiated arginine-vasopressin (AVP), desglycinamide-vasopressin (DGAVP), chicken gonadotropin releasing hormone (GnRH) or carbetocin were injected intracarotidally into rats exposed to a restraint stress for 60 min. The peptide accumulations were determined in 9-13 brain regions and anterior pituitary. In separate experiments the cerebral blood flow was measured. The blood supply to the brain was decreased in stressed animals as indicated by: 1. significant decrease (17-50%) of cerebral blood flow; 2. diminished accumulation of tritiated AVP in the regions lacking a blood-brain barrier (BBB). Consequently, the values of peptide accumulation were corrected for the changed blood supply. Compared with control animals, restraint stress induced a higher accumulation of AVP (+41%), DGAVP (+60%), carbetocin (+81%) and GnRH (+104%).

Animals↗
PubMed1991

Atrial natriuretic peptide augments the blood-brain transfer of water but not leucine and glucose.

Recent evidence predicts an effect of atrial natriuretic peptide (ANP) on the blood-brain transfer of water. To test this prediction, we measured the blood-brain transfer of water, L-leucine, and D-glucose in 9 brain regions of male rats after intravenous injection of 10 pmol ANP. The peptide elicited an increase of the permeability-surface area (PaS) product of labeled water by 28-108% while the PaS products of leucine and glucose remained unchanged. Cerebral blood flow increased 15-48% while cardiac output and plasma volume in brain did not alter, indicating no change of capillary surface area (CSA). Regionally, the CSA varied from 63 cm2/g (striatum) to 97 cm2/g (colliculi) and the fraction of capillaries contributing to the total vascular volume varied from 29% (olfactory bulb/lobe) to 62% (striatum). The blood-brain barrier (BBB) permeability to water (5.7 micron/s) was an order of magnitude higher than to glucose (0.4 micron/s) or to leucine (0.3 micron/s).

Animals↗
PubMed1991

Blood-brain barrier transport under different physiological and pathophysiological circumstances including ischemia.

The blood-brain barrier (BBB) transport of amino acids, glucose and choline was studied under different experimental conditions. The influence of the neuropeptide arginine-vasopressin (AVP) on the transport of leucine and phenylalanine was investigated after peripheral and central nervous application of the peptide and in rats with different endogenous levels of the hormone. AVP elicited changes of the kinetics of the neutral amino acid transport across the BBB accompanied by a decrease of the permeability/surface area (PaS)-product. Also the influence of different nootropic drugs on the BBB transport was investigated under various circumstances of impaired brain function, i.e. after treatment with scopolamine or ethanol and after unilateral carotid artery occlusion. Changes of the kinetics of leucine transport and of the PaS-product of leucine, choline and glucose were found. The results are discussed as part of complex actions of the peptides and nootropics including alterations of the cerebral hemodynamics and brain metabolism.

Amino Acids↗
PubMed1991

Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days.

The efficacy of the traditionally recommended ampicillin (Amp) plus gentamicin (GM) regimen was compared with that of a trimethoprim-sulfamethoxazole (TMP/SMZ)-plus-GM regimen and the adequacy of 14 days total therapy for acute uncomplicated pyelonephritis (AUPN). Eighty-five women hospitalized for AUPN were randomly assigned to receive either Amp, 1 g intravenously (iv) every 6 h for 3 days, then 500 mg orally four times daily, or TMP/SMZ, 160/800 mg iv every 12 h for 3 days, then 160/800 mg orally twice daily. Initially, all patients also received GM every 8 h iv (mean, 606 doses). Antimicrobial resistance necessitated modifying therapy of 14 (32%) of the Amp recipients but of none of the TMP/SMZ recipients (P less than .001). Both regimens produced a satisfactory bacteriologic and clinical response in all cases. Reinfection occurred in 11% of Amp and in 8% of TMP/SMZ recipients. No patient experienced relapsing infection. The TMP/SMZ regimen was less costly and less likely to require modification due to antimicrobial resistance.

Acute Disease↗
PubMed1990

Blood-brain transfer of L-phenylalanine declines after peripheral but not central nervous administration of vasopressin.

To determine whether a previously reported effect of vasopressin on blood-brain transfer of leucine extends to other large neutral amino acids, we measured the regional blood-brain transfer of L-phenylalanine with the integral technique. Intravenous co-injection of L-phenylalanine and arginine vasopressin (30 nmol to 10 pmol) resulted in a decrease of the permeability-surface area (PaS) product of phenylalanine of between 11 and 39%. In addition, the peptide elicited a decrease of the cerebral blood flow of between 11 and 56% combined with a drastic decrease of the cardiac output (32-64%) and an elevation of the blood pressure to approximately 150% of control values. However, we found no changes of the cardiac output, the blood pressure, or the PaS product of phenylalanine after microdialysis (30 min, 5 microliters min-1) of arginine vasopressin (15 mumol L-1) into the dorsal hippocampus, but cerebral blood flow was decreased. The results support the hypothesis that arginine vasopressin receptors at the blood-brain barrier are involved in the regulation of large neutral amino acid transfer from blood to brain and indicate that these receptors are located at the luminal membrane of the endothelial cells.

Animals↗
PubMed1989

beta-Casomorphins alter the intestinal accumulation of L-leucine.

Everted sacs of the rat jejunum change the accumulation of [3H]leucine when beta-casomorphins (BCMs) or synthetic analogs, in a concentration range of 10(-8) mol/l, are coincubated with the amino acid. BCM5 (BCM fragment 1-5, Tyr-Pro-Phe-Pro-Gly) and [D-Ala2]-BCM5-NH2 (Tyr-D-Ala-Phe-Pro-Gly) increase, whereas [D-Pro4]-BCM5 (Tyr-Pro-Phe-D-Pro-Gly) decreases the leucine accumulation and [Arg8]-vasopressin has no effect. No effect of BCM5 could be observed on the accumulation of the space marker [14C]inulin. Specific binding sites for casomorphins were detected microautoradiographically, exclusively at the epithelial cell layer using [3H][D-Pro4]-BCM5 in competition studies as a model. HPLC analysis revealed that under the experimental conditions about 50% of the studied [D-Pro4]-BCM5 was enzymatically degraded and no intact peptide is accumulated within the samples of everted sacs. From the results we postulate a brush-border receptor contact of the BCMs which induces an alteration of the amino acid uptake. A contraluminal binding of the chemical signals is not likely, because there is no evidence for a transepithelial transport of intact BCMs. The observed effects of the BCMs demonstrate as yet unknown peptide-receptor interactions, probably at the brush-border membrane, with subsequent effects on the nutrient supply. Furthermore, the results support the general hypothesis of distinct peptide-receptor interactions in those types of epithelia in which the cells are connected by tight junctions.

Animals↗
PubMed1989

Potassium as a signal for both proliferation and differentiation of rabbit retinal (Müller) glia growing in cell culture.

Retinal glial (Müller) cells were grown from explants of early postnatal rabbit retinae. The resulting monolayers of flat cells were exposed to control media (containing 5.85 mM K+), and to media with enhanced K+ concentrations (10 and 20 mM) or arginine-vasopressin (AVP, 20 micrograms/ml) or epithelial growth factor (EGF, 10 ng/ml). Autoradiographically, protein synthesis was quantified as L-[3H]-lysine incorporation, and DNA synthesis as [3H]-thymidine incorporation. Furthermore, the activity of Na+,K(+)-ATPase was measured radiochemically. Short exposure to either moderately enhanced K+ concentrations (10 mM) or to AVP, stimulated L-[3H]-lysine incorporation into the cells. Long-lasting exposure to either high K+ concentrations (20 mM) or to EGF stimulated [3H]-uptake. The Na+,K(+)-ATPase activity of cell cultures increased with increasing K+ concentration of the media. It is suggested that release of K+ by active neuronal compartments stimulates local protein synthesis of glial cells, resulting in the formation of glial sheaths with active K+ uptake capacity. Strong K+ release may even induce glial proliferation.

Animals↗
PubMed1989

Reversal of scopolamine-induced alterations of choline transport across the blood-brain barrier by the nootropics piracetam and pramiracetam.

The choline transport across the blood-brain barrier was studied in nine brain regions of male Wistar rats after treatment with scopolamine, piracetam and pramiracetam, respectively. 14-Day treatment with scopolamine (0.5 mg/kg/d) elicited an increase of the extraction and the PS-product (permeability-surface area) of choline which was prevented by coinjection of piracetam or pramiracetam (100 mg/kg/d). In addition, the cerebral blood flow was increased by both nootropics. Differences between various brain regions were found in both choline transport and cerebral blood flow. It is supposed from the results that the choline transport is regulated by cholinergic innervation of the brain endothelial cells and that the nootropics used may act via alterations of the brain choline metabolism.

Animals↗
PubMed1988

Pharmacodynamic evaluation of ofloxacin and trimethoprim-sulfamethoxazole in vaginal fluid of women treated for acute cystitis.

Vaginal colonization with Escherichia coli is an integral step in the development of acute cystitis, and persistent vaginal coliform colonization may also be a predisposing step to recurrent urinary tract infections. For this reason, we evaluated antibiotic concentrations in the vaginal fluid, serum, and urine and the vaginal colonization by E. coli of 56 women receiving either ofloxacin (200 mg orally twice a day) or trimethoprim-sulfamethoxazole (TMP-SMX) (160/800 mg orally twice a day) for the treatment of acute cystitis. Ofloxacin and trimethoprim both penetrated into vaginal fluid to a considerably greater extent than sulfamethoxazole. Among 33 patients given ofloxacin, the concentration of the drug in vaginal fluid during one dosage interval ranged from 1.6 to 21.6 micrograms/ml. In 21 women given TMP-SMX the range of drug concentrations in vaginal fluid was 2.6 to 32.5 micrograms/ml for TMP and 1.0 to 6.2 micrograms/ml for SMX. Treatment with both ofloxacin and TMP-SMX remarkably reduced vaginal colonization by E. coli during and up to 30 days after therapy. For the ofloxacin-treated women, eradication of vaginal E. coli was associated with a high ratio of drug concentration in vaginal fluid to that in serum. We conclude that ofloxacin and TMP both achieve high concentrations in vaginal fluid and are equally successful in eradicating E. coli from the vagina.

Administration, Oral↗
PubMed1988

Kinetics of regional blood-brain barrier transport of L-leucine in Brattleboro rats.

The transport of L-leucine across the blood-brain barrier was studied in heterozygous (NON-DI) and homozygous (DI) Brattleboro male rats using the carotid bolus injection technique. Furthermore, general hemodynamic parameters and cerebral blood flow were measured. No significant hemodynamic differences were found between DI and NON-DI rats except for a 22% lower cerebral blood flow in the olfactory bulb of DI rats. The maximum velocity of L-leucine transport (Vmax), the half saturation constant (Km) and the nonsaturable transport constant (KD) were estimated in nine brain regions. The Vmax values of NON-DI rats were by 28% to 64% lower than those of DI rats. The calculated regional Km values of NON-Di rats were by 14% to 58% lower. These differences were most pronounced in hippocampus and hypothalamus. The results support the suggestion that endogenous vasopressin may alter the large neutral amino acid transport across the blood-brain barrier.

Animals↗