Biomedical subjects
Linda Jørgensen
Publications and source records attributed to Linda Jørgensen.
Persistent arterial hyperammonemia increases the concentration of glutamine and alanine in the brain and correlates with intracranial pressure in patients with fulminant hepatic failure.
In this prospective study of patients with fulminant hepatic failure (FHF), we tested the hypothesis that arterial hyperammonemia results in cerebral accumulation of the osmotic active amino acids glutamine and alanine, processes that were expected to correlate with intracranial pressure (ICP). By using in vivo brain microdialysis technique together with ICP monitoring in 17 FHF patients (10 females/7 males; median age 49 (range 18 to 66) years), we found that arterial ammonia concentration correlated to brain content of glutamine (r=0.47; P<0.05) but not to alanine. A persisting high arterial ammonia concentration (above 200 micromol/L) characterized patients who developed high ICP (n=8) while patients who did not experience surges of increased ICP (n=9) had a decline in the ammonia level (P<0.05). Moreover, brain glutamine and alanine concentrations were higher at baseline and increased further in patients who developed intracranial hypertension compared with patients who experienced no surges of high ICP. Brain glutamine concentration increased 32% from baseline to 6536 (697 to 9712) micromol/L (P<0.05), and alanine 44% from baseline to 104 (81 to 381) micromol/L (P<0.05). Brain concentration of glutamine (r=0.59, P<0.05), but not alanine, correlated to ICP. Also arterial ammonia concentration correlated to ICP (r=0.73, P<0.01). To conclude, this study shows that persistence of arterial hyperammonemia is associated with profound changes in the cerebral concentration of glutamine and alanine. The elevation of brain glutamine concentration correlated to ICP in patients with FHF.
In-depth characterization of CGRP receptors in human intracranial arteries.
The purpose of the present study was to characterize the effects of human (h) alpha- and beta-calcitonin gene-related peptide (CGRP) on intracranial arteries from man and to investigate the presence of mRNA for the calcitonin receptor like receptor (CRLR) and the receptor activity modifying proteins (RAMPs) 1, 2 and 3, in cerebral and middle meningeal arteries with and without endothelium, in microvessels and in the endothelial cells isolated from the human basilar artery. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of CRLR, RAMP 1, RAMP 2 and RAMP 3 in cerebral and middle meningeal arteries with and without endothelium as well as in microvessels and in the endothelial cells. Human and rat alpha- and beta-CGRP, amylin, adrenomedullin and [acetamidomethyl-Cys(2,7)]human CGRP induced strong concentration-dependent relaxation of human cerebral and middle meningeal arteries. Removal of the endothelium neither changed the maximum relaxant response nor the pIC(50) values for alpha- and beta-CGRP as compared to the responses in arteries with an intact endothelium. Human alpha-CGRP-(8-37) caused a shift of h alpha- and h beta-CGRP-induced relaxations in cerebral and middle meningeal arteries. Calculation of pK(B) values revealed that h alpha-CGRP-(8-37) could not significantly discriminate between relaxations induced by h alpha-CGRP (pK(B) around 6.8) and h beta-CGRP (pK(B) around 5.4). There was no significant difference in pK(B) value of h alpha-CGRP-(8-37) on h beta-CGRP-induced relaxation of human cerebral and middle meningeal arteries with and without endothelium. In conclusion, our molecular and pharmacological data support the existence of a single type of CGRP(1) receptors in the human intracranial circulation.