It has been suggested that the induction of lipocortin-1, a phospholipase A2-inhibitory protein, may mediate the anti-inflammatory action of glucocorticoids. We assessed the production of prostaglandin E2, thromboxane B2, and leukotriene B4 and the expression of lipocortin-1 in different populations of blood leukocytes and in alveolar macrophages (obtained by bronchoalveolar lavage) from patients with inflammatory lung diseases (bronchial asthma, n = 21; interstitial lung disease, n = 6) undergoing glucocorticoid treatment at clinically effective doses. No inhibition of eicosanoid production was observed in either whole blood or single populations of blood leukocytes (granulocytes and monocytes) stimulated with ionophore A-23187, N-formyl-L-methionyl-L-leucyl-L-phenylalanine, or zymosan. Conversely, eicosanoid production from alveolar macrophages (assessed in 9 cases) was significantly inhibited by glucocorticoids. After ionophore stimulation, eicosanoid production was as follows (in ng/ml): prostaglandin E2, 0.19 +/- 0.06 and 0.06 +/- 0.01; thromboxane B2, 2.9 +/- 0.9 and 0.5 +/- 0.1; leukotriene B4, 6.6 +/- 1.1 and 3.6 +/- 1.0, before and after treatment, respectively (P < 0.05 for all differences). Lipocortin-1 expression, determined by Western blot and enzyme immunoassay, was significantly (P < 0.05) stimulated in alveolar macrophages, but not in blood leukocytes, by glucocorticoid treatment. These results indicate that alveolar macrophages, at variance from blood leukocytes, are the most likely cell target for glucocorticoid-induced eicosanoid inhibition and lipocortin expression. We suggest that cell responsiveness to glucocorticoids is acquired during differentiation from monocyte to tissue macrophage.
Brante in 1949 10 earned out the first complete study of the lipid eomposition of human intraeranial tumors. He analyzed 11 cases of gliomas and found that total lipids aecounted for 15 to 85% of the dry weight, the dry weight being about 15% of the weight of fresh tissue. Phospholipids made up about 10%, total cholesterol 2% (3/4 of which was in the free form), and cerebrosides 2-M%. There were only traces of diglycerides and no difference was found between the several types of gliomas analyzed: only in one case of gliomatous teratoma the percentage of phospholipids decreased to 5%, while that of diglycerides increased to 12%. Brante ascribed this difference to a long period of fixation in formalin, which produces a breakdown of glyeero-phospholipids. Besides the tumors of mesodermaI origin, Brante evaluated the lipid eomposition of six meningeomas. The dry weight was calculated as being between 14% and 17% of the total weight, while the total lipid content was between 15 and 25% of the dry weight. Phospholipids were about 9%, total cholesterol 2% (2/3 in free form), and cerebrosides 1--8%. Brante did not consider the differenee in lipid composition between gliomas and meningiomas to be significant. Neurinomas --8 cases of acoustic neurinoma --had a lower lipid content than the other intraeranial tumors; about 15% of the dry weight. In the only case of haemangioma analyzed, phospholipids were only 6%, while total cholesterol was near 8% (only 1/3 of it in the free form), the same proportion as in serum cholesterol. No traces of cerebrosides were found. The lipid eomposition of one eosinophileous granuloma was found to be very similar to that of the haemangioma.Brante also studied the lipid composition of normal human piaaraehnoidea, which contains 82% lipids, with 8% phospholipids and a large unidentified fraction, supposed to be neutral fat. No traces of eholesteroI and eerebrosides were found.In the normal human adult brain, Brante found the following composition: dry weight 15% of total flesh weight, total lipids 85%, phospholipids 20%, cholesterol 5% (all in the free form) and eerebrosides 4%.
Endothelin (ET) is considered one of the most potent vasoconstrictor polypeptides; several experimental studies have suggested its possible role in the pathogenesis of arterial vasospasm after subarachnoid haemorrhage (SAH). Previously reported data on plasma and CSF levels of endothelin in patients with a diagnosis of SAH have been controversial. Cisternal endothelin CSF levels and the possibility that they could be related to vasospasm and other clinical patterns of SAH were investigated. CSF samples were obtained from 55 patients admitted after angiographic diagnosis of intracranial aneurysm. Levels of ET-1 and ET-3 were measured through radioimmunoassay technique.
We determined arachidonic acid (AA) cyclooxygenase metabolic profiles in specimens of human intracranial tumors (gliomas and meningiomas) and, when available, normal brain tissue. Samples were collected at surgery and immediately frozen in liquid nitrogen. The five stable metabolites of AA (PGE2, PGD2, PGF2 alpha, 6-keto-PGF1 alpha and TXB2) were measured by high-resolution gas chromatography-mass spectrometry after ex vivo metabolism of endogenous AA by tissue homogenates. The absolute amounts of AA metabolites varied widely between samples, though meningiomas and gliomas showed characteristic profiles. Compared to the slow-growing benign meningiomas, the rapidly-growing infiltrating gliomas had higher synthesis of TXA2 (reported as a procancer metabolite) and lower synthesis of PGD2 and PGI2 (reported as anticancer metabolites). A higher overall synthesis capacity, preferentially toward TXA2, was found in glioblastomas than in non-pathological brain tissue.
Tissue samples from 57 patients with neuroepithelial tumors (25 glioblastomas, 18 anaplastic astrocytomas, and 14 astrocytomas) were analyzed in order to evaluate the presence of estrogen, progesterone, glucocorticoid, and androgen receptors. Glucocorticoid- and androgen-specific binding proteins were present in 38.6% and 21.6% of the cases, respectively. Only a few tumors showed estrogen or progesterone receptors. A correlation was found between grade of anaplasia, patient's sex and age, and presence of glucocorticoid and androgen receptors. The biological role of these two receptors was investigated in 10 primary cell cultures derived from neuroepithelial tumors. For this purpose, dexamethasone and testosterone were added to culture medium at different concentrations (from 50 to 0.016 micrograms/ml). A significant stimulation of the cell growth was observed in four of five glucocorticoid receptor-positive cultures when dexamethasone in doses ranging from 2 to 0.016 microgram/ml was added to the culture. No modulation of the growth was observed in glucocorticoid receptor-negative cultures at the same doses. Higher dexamethasone doses induced a significant decrease of the growth index independently from the glucocorticoid receptor status. All of the cultures tested for testosterone activity were negative for androgen receptors. This hormone induced an inhibition of the growth index at doses ranging from 50 to 0.4 micrograms/ml. The data suggest that neuroepithelial tumors contain specific glucocorticoid and androgen binding proteins. Glucocorticoid receptors modulate the growth of cultured neuroepithelial tumors in the presence of different concentrations of dexamethasone.
Leukotrienes derive from arachidonic acid metabolism via the lipoxygenase pathway and modulate several cellular events. In the central nervous system, leukotrienes are mainly synthesized in the gray matter and in vascular tissues. Their production is enhanced in ischemic conditions and in experimental subarachnoid hemorrhage (SAH). Previous studies have indicated the ability of the leukotrienes C4 and D4 to constrict arterial vessels in vivo and in vitro and have suggested their involvement in the pathogenesis of cerebral arterial spasm. In the present study, the authors measured lumbar and cisternal cerebrospinal fluid (CSF) levels of leukotriene C4 in 48 patients who had suffered aneurysmal SAH. In 12 of the cases, symptomatic and radiological spasm was evident. The mean lumbar CSF level of immunoreactive-like activity of leukotriene C4 (i-LTC4) was significantly higher (p less than 0.005) than in control cases, while the cisternal CSF level was higher than the lumbar mean concentration (p less than 0.005). Patients presenting with vasospasm had significantly higher levels of i-LTC4 compared to patients without symptomatic vasospasm. This is the first report concerning monitoring of i-LTC4 levels in the CSF after SAH. The results of this study suggest that: 1) metabolism of arachidonic acid via the lipoxygenase pathway is enhanced after SAH; 2) the higher cisternal CSF levels of i-LTC4 may be part of the biological response in the perianeurysmal subarachnoid cisterns after the hemorrhage; and 3) the higher CSF levels of i-LTC4 in patients presenting with vasospasm suggest that a relationship exists between this compound and arterial spasm and/or reflect the development of cerebral ischemic damage.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.