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Q R Smith

Publications and source records attributed to Q R Smith.

67 records · Page 4Linked to original sources
PubMed1984

Brain uptake of a food dye, erythrosin B, prevented by plasma protein binding.

Although food colors have been held responsible for several behavioral disorders and do affect neuronal function when directly applied, there is no information on whether significant quantities of the dyes appear in the brain after consumption or parenteral administration. [14C]erythrosin B was administered directly into the circulation of mature rats and radioactivity was measured thereafter in brain regions at several times. Although insignificant parenchymal radioactivity was detected in brains perfused with dye in whole blood, significant concentrations of [14C]erythrosin B were detected in all brain regions when perfused with protein-free Ringers, as predicted from the octanol-water partition coefficient of the dye. Thus, significant brain uptake of intravascular dye is normally prevented by its binding to plasma protein (greater than 99% bound) and by the blood-brain barrier impermeability to the dye-protein complex. Sensitivity to food dyes such as erythrosin B in some individuals may reflect altered plasma protein binding capacity, which can vary with age and disease.

Animals↗
PubMed1984

Kinetic analysis of L-leucine transport across the blood-brain barrier.

Unidirectional L-leucine influx across cerebral capillaries was measured at different concentrations with an in situ rat brain perfusion technique, which has several advantages over presently-used methods such as the Brain Uptake Index (BUI) technique. The maximal influx rate (Vmax) and half-saturation concentration (Km) equaled 1.07 +/- 0.02 X 10(-3) mumol X s-1 X g-1 and 0.026 +/- 0.002 mumol X ml-1, respectively, for the saturable component, and the constant for non-saturable influx equaled 6.8 +/- 1.4 X 10(-5) s-1. These values differ by 3-4-fold from respective values obtained with the BUI technique.

Animals↗
PubMed1984

Carrier-mediated transport of chloride across the blood-brain barrier.

36Cl concentrations in each of eight brain regions and in cisternal cerebrospinal fluid (CSF) were determined 30 min after the intravenous injection of 36Cl in dialyzed-nephrectomized rats with plasma Cl concentrations between 14 and 120 mumol X ml-1. CSF 36Cl exceeded 36Cl concentrations in brain extracellular fluid. The calculated blood-to-brain transfer constants for Cl, kCl, ranged from 1.8 X 10(-5) S-1 at the parietal cortex to 3.8 X 10(-5) S-1 at the thalamus-hypothalamus. kCl fell by 42-62% when mean plasma [Cl] was elevated from 16 to 114 mumol X ml-1. Brain uptake of [14C]mannitol or of 22Na was independent of plasma [Cl], but 22Na influx into CSF fell when plasma [Cl] was reduced. Cl flux into brain and CSF could be represented by Michaelis-Menten saturation kinetics, where, for the parietal cortex, Km = 43 mumol X ml-1 and Vmax = 2.5 X 10(-3) mumol X S-1 X g-1, and for CSF Km = 68 mumol X ml-1. At least 80% of 36Cl influx into the parietal cortex was calculated to occur at the cerebrovascular endothelium, whereas the remainder was derived from tracer that first entered CSF. The CSF contribution was greater at brain regions adjacent to cerebral ventricles. The results show that Cl transport at the cerebrovascular endothelium as well as at the choroid plexus epithelium is a saturable concentration-dependent process, and that the CSF is a significant intermediate pathway for Cl passage from blood to brain.

Animals↗
PubMed1984

An in situ brain perfusion technique to study cerebrovascular transport in the rat.

The right cerebral hemisphere of the rat was perfused in situ by retrograde infusion of HCO3 saline or blood into the right external carotid artery. Infusion rate was adjusted to minimize the contribution of systemic blood to flow in the hemisphere. During perfusion with whole or artificial blood, regional cerebral blood flow and blood volume were comparable to respective values in the conscious rat, whereas perfusion with HCO3 saline increased regional flow three- to fourfold due to the low viscosity of the saline perfusate. Perfusion with whole blood for 300 S or with HCO3 saline for 60 S did not alter the permeability of the blood-brain barrier. Cerebrovascular permeability coefficients of eight nonelectrolytes ranged from 10(-8) to 10(-4) cm X S-1 and were directly proportional to the octanol-water partition coefficient of the solute. Thus the in situ brain perfusion technique is a sensitive new method to study cerebrovascular transfer in the rat and permits absolute control of perfusate composition.

Animals↗
PubMed1982

Kinetic analysis of [36Cl]-, [22Na]- and [3H]mannitol uptake into the in vivo choroid plexus-cerebrospinal fluid brain system: ontogeny of the blood brain and blood-CSF barriers.

The kinetics of penetration of radioactive [36Cl]-, [22Na]- and [3H]mannitol into the choroid plexus-CSF brain system was investigated in 1-week, 2-week and adult Sprague-Dawley rats. For adult rats (5 weeks), 36Cl and 22Na uptake by the choroid plexus of lateral ventricle (LVCP) and fourth ventricle (4VCP) resolved into a fast component (t1/2 0.02 - 0.05 h) representing isotope distribution within the extracellular and residual erythrocyte compartments, and a slow component (t1/2 0.8 - 1.9 h) representing isotope movement into the epithelial cell compartment. From steady-state distribution data, choroid cell [Cl] in both LVCP and 4VCP was calculated to be 67 mmol/kg cell H2O, a level nearly 4 times greater than that predicted by the membrane potential for passive distribution. In 1-week immature rats cell [Cl] and [Na] in the choroid plexuses were even greater than the corresponding levels in adults, probably because ion transport across the basolateral membrane is not yet coupled with ion movement from cell to CSF. In mature rats the 36Cl and 22Na uptake into the CSF resolved into 2 components (t1/2 0.18 h, fractional volume 0.24 and t1/2 1.2 h, fractional volume 0.76); however, the fast component of CSF uptake, which likely represents isotope movement across the choroid plexuses, was negligible in the 1-week animals. Permeability-surface area products (PA) were determined for the blood-CSF barrier (i.e. the choroid plexuses) as well as the blood-brain barrier (cerebral cortex and cerebellum). The PA values for 36Cl and 22Na as determined by the fast component of CSF uptake (choroid plexus secretion?) were an order of magnitude less in the 1-week rats than in adults. In contrast, the effective permeability of the blood-CSF barrier as well as the blood-brain barrier, as evaluated by changes in PA of [3H]mannitol, decreased steadily with advancing age.

Age Factors↗
PubMed1981

Uptake of 36Cl and 22Na by the choroid plexus-cerebrospinal fluid system: evidence for active chloride transport by the choroidal epithelium.

Cl and Na transport by the lateral ventricle (LVCP) and fourth ventricle (4VCP) choroid plexuses were examined by kinetic analysis of 36Cl and 22Na uptake into the choroid plexus-CSF system of the adult rat. Both radioisotopes required most than 5 h to reach steady-state distribution in the in vivo choroid plexuses and CSF after intraperitoneal injection. Whereas the LVCP and 4VCP 36Cl steady-state spaces were comparable (55--56%), the 4VCP 22Na space (39%) tended to be greater than the LVCP 22Na spaces (36%). No evidence for inexchangeable Cl or Na was found for the choroid plexuses; the radioisotopic and chemical spaces were not significantly different. Choroid plexus 36Cl and 22Na uptake curves were resolved into two components, a fast component (t1/2 0.02--0.05 h) and a slow component (t1/2 0.85--1.93 h). By analysis of the distribution of [3H]inulin, [3H]mannitol, and 51Cr-tagged erythrocytes within the choroid plexuses, the fast component of 36Cl and 22Na uptake was found to represent extracellular and erythrocyte contributions to the tissue radioactivity, whereas the slow component represented isotope movement into the epithelial cell compartment. The calculated cell [Cl] of LVCP and 4VCP, 67 mmol/kg cell water, was 3.9 times greater than that predicted by the membrane potential for passive distribution. It is postulated that Cl is actively transported into the choroid epithelial cell across the basolateral membrane; the energy source for active Cl transport may be the Na electrochemical potential gradient (approximately 90 mV), which is twice that of the Cl electrochemical potential gradient (approximately 45 mV).

Animals↗
PubMed1980

Effect of carbonic anhydrase inhibitors and acidosis in choroid plexus epithelial cell sodium and potassium.

To elucidate the mechanism by which carbonic anhydrase inhibitors block fluid production by the choroid plexus (CP), Na-K transport by the rat choroidal epithelium was investigated by measuring acetazolamide- and benzolamide-induced changes in cell [K] and [Na]. Although plasma and cerebrospinal fluid [K] and [Na] were not significantly altered after 1 hr of drug treatment, both acetazolamide (20 mg/kg) and benzolamide (40 mg/kg) decreased in vivo CP cell [Na] by 11 to 18 mmol/kg of cell H2O and substantially increased cell [K] by 25 to 35 mmol. Compensatory artificial respiration to control blood pH blocked the drug-induced effects of cell electrolytes. Furthermore, acetazolamide (5 x 10(-5) and 5 x 10(-4) M) did not significantly alter cell [Na] or [K] in in vitro incubations of CP, although cell [K] tended to decrease in a drug concentration-dependent manner. Thus, carbonic anhydrase inhibitors have no direct effect on the gradient for Na or K between choroid cell fluid and surrounding extracellular fluid. It is proposed that the carbonic anhydrase inhibitors reduced Na entry into the choroid epithelium across the basolateral membrane concurrent with a decrease in the rate of the apical membrane Na-K pump. To investigate whether the drug-induced extracellular acidosis changed cell electrolyte levels directly or indirectly, in vitro CP tissue incubations were performed in which the pH of the artificial cerebrospinal fluid was varied from 7.24 to 7.44. CP cell [K] increased by 20 mmol/kg of H2O and cell [Na] fell by 10 when bathing medium pH was lowered from 7.39 to 7.24. We postulate that the lowered blood pH directly stimulates K uptake and Na efflux from the CP cell, although an indirect effect of acidosis, either through an alteration of levels of circulatory hormones or of autonomic input to the CP, cannot be excluded.

Acetazolamide↗
PubMedDate not supplied

Two-phase [11C]L-methionine PET in childhood brain tumors.

Thirteen children (1.8-15.8 years of age) with brain tumors were studied with [11C]L-methionine positron emission tomography (METPET). Patients were injected intravenously with tracer before a baseline PET scan was obtained. To assess the sensitivity of [11C]L-methionine uptake to competitive inhibition, 10 patients received oral L-phenylalanine (100 mg/kg); 1 hour later, a second METPET was obtained. Subjective assessment of [11C]L-methionine uptake closely paralleled results of quantitative examination (r = 0.81). [11C]L-methionine uptake in tumor-containing brain was increased in 11 patients (mean ratio of [11C] radioactivity in tumor to normal brain: 1.5 +/- 0.57; range: 1.13-2.98). Increased tracer uptake occurred in ependymomas (3), medulloblastoma (1), and astrocytomas (5), but was less intense in low-grade tumors. L-phenylalanine reduced L-methionine uptake (25-69%) in 70% of studies. L-methionine uptake was not sensitive to competitive inhibition in brain radiation injury. Two-phase METPET is of potential value in difficult clinical situations evident in children with brain tumors, including the differential diagnosis of tumor recurrence and cerebral radiation injury.

Adolescent↗
PubMedDate not supplied

Fatty acid uptake and incorporation in brain: studies with the perfusion model.

The contributions of individual components of blood to brain [14C]palmitate uptake and incorporation were studied with the in situ brain perfusion technique in the pentobarbital-anesthetized rat. With whole-blood perfusate, brain unacylated [14C]palmitate uptake was linear with time and extrapolated to zero at T = 0 s of perfusion. Tracer accumulated in brain with a blood-to-brain transfer coefficient of 1.8 +/- 0.1 x 10(-4) mL/s/g (whole cerebral hemisphere). Incorporation into brain lipids was rapid such that approximately 40% of tracer in brain at 45 s of perfusion was in cerebral phospholipids and neutral lipids. Similar rates of uptake were obtained during unacylated [14C]palmitate perfusion in whole rat plasma, serum, or artificial saline containing 2-3% albumin, suggesting that albumin has a key role in determining [14C]palmitate uptake in brain. The excellent match in brain uptake rates between whole blood and albumin-containing saline fluid suggests that the perfusion technique will be useful method for quantifying the individual contributions of blood constituents and albumin binding on brain [14C]palmitate uptake.

Animals↗