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K Pettigrew

Publications and source records attributed to K Pettigrew.

25 records · Page 2Linked to original sources
PubMed1990

Dexamethasone effects on the distribution of water and albumin in cold-injury cerebral edema.

To evaluate the effectiveness of steroids in the treatment of traumatic cerebral edema, we have hypothesized that the distribution of water and RISA is diminished by Dex and have experimentally tested this proposition with the rat model of cortical cold injury. Dex was found to have no effect on the water content of normal brain. The cold injury significantly increased the water content of only the right middle forebrain in untreated rats; in contrast, the increase in water content in the right middle forebrain after cold injury was small and insignificant in Dex-treated rats. Dex diminished the distribution of RISA in the tissue immediately adjacent to the primary lesion but did not affect RISA distribution within the lesion or the remainder of the brain. These findings suggest that steroids do not alter the distribution of water and albumin within cerebral tissue that has been heavily damaged and that steroids do affect these processes in the less traumatized tissue immediately surrounding the primary lesion.

Animals↗
PubMed1989

Refinement of the kinetic model of the 2-[14C]deoxyglucose method to incorporate effects of intracellular compartmentation in brain.

A translocase to transport hexose phosphate formed in the cytosol into the cisterns of the endoplasmic reticulum, where the phosphatase resides, is absent in brain (Fishman and Karnovsky, 1986). 2-Deoxyglucose-6-phosphate (DG-6-P) may therefore have limited access to glucose-6-phosphatase (G-6-Pase), and transport of the DG-6-P across the endoplasmic reticular membrane may be rate limiting to its dephosphorylation. To take this compartmentation into account, a five-rate constant (5K) model was developed to describe the kinetic behavior of 2-deoxyglucose (DG) and its phosphorylated product in brain. Loss of DG-6-P was modeled as a two-step process: (a) transfer of DG-6-P from the cytosol into the cisterns of the endoplasmic reticulum; (b) hydrolysis of DG-6-P by G-6-Pase and subsequent return of the free DG to the precursor pool. Local CMRglc (LCMRglc) was calculated in the rat on the basis of this model and compared with values calculated on the basis of the three-rate constant (3K) and the four-rate constant (4K) models of the DG method. The results show that under normal physiological conditions all three models yield values of LCMRglc that are essentially equivalent for experimental periods between 25 and 45 min. Therefore, the simplest model, the 3K model, is sufficient. For experimental periods from 60 to 120 min, the 4K and 5K models do not correct completely for loss of product, but the 5K model does yield estimates of LCMRglc that are closer to the values at 45 min than those obtained with the 3K and 4K models.

Animals↗
PubMed1988

Local cerebral glucose utilization in controlled graded levels of hyperglycemia in the conscious rat.

Local cerebral glucose utilization assayed by the [14C]deoxyglucose ([14C]DG) method and calculated by means of its operational equation with values for the rate constants and lumped constant determined in rats under physiological conditions remains relatively stable with variations in arterial plasma glucose concentration within the normoglycemic range. Large changes in arterial plasma glucose level may, however, significantly alter the values of these constants and lead to artifactual results. Values for the lumped constant have been measured and reported for a wide range of arterial plasma glucose concentrations ranging from hypoglycemia to hyperglycemia in the rat (Schuier et al., 1981; Suda et al., 1981; Pettigrew et al., 1983). In the present study we have redetermined the rate constants in rats with arterial plasma glucose levels clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM) by a glucose clamp technique. The rate constants for the transport of DG from plasma to brain, K1*, and its phosphorylation in tissue, k3*, were found to decline with increasing plasma glucose levels, while the rate constant for its transport back from brain to plasma, k*2, remained relatively unchanged from its value in normoglycemia. These rate constants were used together with the previously determined values for the lumped constants to calculate local rates of cerebral glucose utilization in three groups of rats in which arterial plasma glucose levels were clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM). Average glucose utilization in the brain as a whole was unchanged in hyperglycemia from the values calculated in normoglycemic rats with the standard normal set of constants. Changes in the rate of glucose utilization were found, however, in the hypothalamus, globus pallidus, and amygdala during hyperglycemia.

Animals↗
PubMed1987

Effects of insulin on hexose transport across blood-brain barrier in normoglycemia.

The effects of insulin on 3-O-[14C]methylglucose transport across the blood-brain barrier (BBB) were studied in conscious rats under steady-state normoglycemic conditions. The [14C]methylglucose was infused intravenously at a constant rate, and animals were killed at various times between 5 and 30 min after the initiation of the infusion. The time course of the arterial plasma concentration of [14C]methylglucose was determined in timed arterial blood samples taken during the infusion. Local cerebral tissue concentrations of [14C]methylglucose at the time of killing were determined by quantitative autoradiography of brain sections. The rate constants for inward and outward transport of [14C]methylglucose across the BBB, K1, and k2, respectively, were estimated by a least-squares, best-fit of a kinetic equation to the measured time courses of plasma and tissue concentrations. K1 and k2 were reduced by an average of 24 and 31%, respectively, in gray matter and 7 and 16% in white matter from values estimated similarly in normal insulinemic control rats. The equilibrium distribution ratio, K1/k2, for [14C]methylglucose in brain increased by approximately 10-11% in the hyperinsulinemic animals. Because 3-O-[14C]methylglucose shares the same carrier that transports glucose and other hexoses across the BBB, these results suggest that hyperinsulinemia decreases the rate constants for transport but increases the distribution space for hexoses in brain. These effects are, however, quite small and are probably minor or negligible when compared with the major effects of insulin in other tissues.

3-O-Methylglucose↗
PubMed1977

Evaluation of the utility of air-dried whole mounts for quantitative electron microprobe studies of platelet dense bodies.

A variety of electronmicroscope techniques have been used to examine how the air-drying process may affect the dense bodies in whole mounts of platelets. (a) Selected-area-diffraction and electron microprobe studies suggest that the air-drying process can result in the formation of crystalline precipitates of sodium chloride on grid films and platelets. However, no crystals were detected in the calcium-and-phosphorus-containing matrix of dense bodies. (b) Tilting studies show that dense bodies in human platelets are spherical or ellipsoidal in shape. Dense bodies in rabbit platelets, in contrast, appear flattened in a horizontal plane. (c) Human-platelet dense bodies probed with a small (20 nm diameter) spot vary widely in their peak/background ratios for calcium and phosphorus-a finding that suggests that the two elements may not be evenly distributed throughout the dense-body matrix. Nevertheless, when dense bodies are probed with a larger (200 nm diameter) spot, they do not appear to differ appreciably among themselves in their calcium or phosphorus content. The data suggest that with human platelets, air drying may be a preparative procedure which permits comparison by microprobe techniques of dense-body matrix content in platelet populations.

Animals↗