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K U Chu S Higashide B M Evers S Rajaraman J Ishizuka C M Townsend Jr J C Thompson 《Annals of surgery》1994,220(4):570-577
OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents. 相似文献
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J W Rose H Lorberboum-Galski D Fitzgerald R McCarron K E Hill J J Townsend I Pastan 《Journal of neuroimmunology》1991,32(3):209-217
IL2-PE40 is a chimeric protein composed of human interleukin-2 (IL2) genetically fused to a modified form of Pseudomonas exotoxin lacking the cell recognition domain. IL2-PE40 is cytotoxic for IL2 receptor-bearing lymphocytes in culture and can inhibit activation of T cells in vivo. IL2-PE40 can significantly diminish antigen-stimulated proliferation of lymphocytes sensitized to myelin basic protein. Intraperitoneal administration of IL2-PE40 not only markedly inhibits the clinical manifestations of adoptively transferred relapsing experimental allergic encephalomyelitis but also dramatically reduces both inflammation and demyelination characteristic of the disease. 相似文献
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By convention, establishing a physiologic role for a gut peptide requires demonstration of biologic activity that can be reproduced by exogenous administration of the peptide in amounts that yield plasma concentrations that are not higher than those found after a meal. We have tested the hypothesis that the combined action of two inhibitory peptides may lower the effective doses of each. We further hypothesize that combined peptide responses may be responsible for the action of peptide hormones that have been difficult to demonstrate as physiologically relevant mediators, when examined as independently acting substances. In conscious dogs prepared with chronic pancreatic cannulas, stimulated pancreatic exocrine secretions were depressed in a dose-related manner by intravenous infusions of calcitonin (CT) and calcitonin gene-related peptide (CGRP). Doses of 2.0 nmol/kg/hr of both CT and CGRP yielded maximal inhibition of stimulated secretions of both bicarbonate (greater than 85% inhibition) and protein (greater than 55% inhibition). The lowest effective dose for either CT or CGRP, given alone, was 0.75 nmol/kg/hr, but when infused simultaneously, each at the subthreshold dose of 0.50 nmol/kg/hr, significant inhibition of protein and bicarbonate secretion was achieved. Combined infusions of the submaximal dose of 0.75 nmol/kg/hr resulted in an enhanced inhibitory response. To prove that this effect is not simply combined activation of a common receptor, we tested peptide YY (0.1 to 0.5 nmol/kg/hr) combined with CGRP and obtained similar results. Because a meal simultaneously releases a large number of active peptides, we speculate that such potentiated responses do occur physiologically. Cooperative interaction with other agents may be the primary mode of action for certain gut peptides. 相似文献
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Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk 总被引:1,自引:0,他引:1
Olmer M; Renucci JE; Planells R; Bouchouareb D; Purgus R 《Nephrology, dialysis, transplantation》1997,12(4):691-693
Conventional risk factors have very low predictive power in identifying
haemodialysis patients at high risk of vascular accidents. A role for
apolipoprotein E isotypes was looked for in a small, but rigorously
defined, cohort of longterm haemodialysis patients. In individuals with
high vascular risk, as identified by higher common carotid intima/media
thickness, we found an excess of apolipoprotein E4 alleles. This
preliminary result requires confirmation in large patient cohorts.
相似文献
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Panic disorder is a chronic and disabling condition that is often accompanied by other psychiatric and medical conditions. The serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been used effectively with panic disorder (PD) and conditions in which panic attacks frequently occur. Escitalopram is the most selective SSRI and a variety of evidence suggests it is of great value in the treatment of panic disorder. In this paper, we review the theoretical and practical implications of its use. 相似文献
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Increased expression of certain glutathione S-transferase (GST) isoenzymes has frequently been associated with the development of resistance to alkylating agents and other classes of antineoplastic drugs in drug-selected cell lines. The question arises whether this phenomenon is causal or is a stress-induced response associated with drug resistance in these cell lines. We have constructed mammalian expression vectors containing the human GST mu and GST alpha 2 (Ha2) cDNAs and stably transfected them into the human breast cancer cell line MCF-7. Whereas the parental and pSV2neo-transfected cell lines display low GST activity, three individual transfected clones were identified in each group that expressed either GST mu or GST alpha 2. The range of GST activities was similar to those observed in cells selected for anticancer drug resistance. The GST mu specific activities were 56, 150, and 340 mlU/mg, compared with 10 mlU/mg of endogenous GST mu in control lines. Specific activities in GST alpha 2-transfected clones were 17, 28, and 52 mlU/mg, compared with no detectable alpha class GST in control lines. These clonal lines and the parental and pSV2neo-transfected control lines were tested for sensitivity to antineoplastic agents and other cytotoxic compounds. The clones with the highest activity in each group were 1.7-fold (GST alpha 2) to 2.1-fold (GST mu) resistant to the toxic effects of ethacrynic acid, a known substrate for GSTs. However, the GST-transfected cell lines were not resistant to doxorubicin, L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, cisplatin, chlorambucil, or the GST substrates 1-chloro-2,4-dinitrobenzene or tert-butyl hydroperoxide. Thus, although L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, chlorambucil, tert-butyl hydroperoxide, and 1-chloro-2,4-dinitrobenzene are known to be metabolized by glutathione-dependent GST-catalyzed reactions, there was no protection against any of these agents in MCF-7 cell lines overexpressing GST mu or GST alpha 2. We conclude that, at the levels of GST obtained in this transfection model system, overexpression of GST mu or GST alpha 2 is not by itself sufficient to confer resistance to these anticancer agents. These studies do not exclude the possibility that GST may be a marker of drug resistance or that other gene products not expressed in MCF-7 cells might cooperate with GST to confer drug resistance. 相似文献