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991.
The ability of increased neuronal activity to accelerate catecholamine biosynthesis and tyrosine hydroxylase activity in the rat brain was tested. Noradrenergic neurons of the locus coeruleus (LC) were stimulated unilaterally at 20 Hz and the cortex and/or hippocampus from stimulated and contralateral (control) sides of the brain were analyzed and compared. Rats were injected with a dopa decarboxylase inhibitor and the accumulation of endogenously synthesized dopa used as an in vivo index of tyrosine hydroxylase activity. Thirty minutes after termination of 15 min of unilateral LC stimulation, dopa accumulation was 35% greater in the ipsilateral cortex + hippocampus. In untreated rats, at the end of 15 min of LC stimulation, there was an ipsilateral depletion of cortical norepinephrine (NE) which recovered within 30 min. When rats were injected with [3H]tyrosine (i.v.) during this half-hour recovery period, a poststimulation increase in [3H]catecholamine synthesis was observed in both the cortex (63%) and hippocampus (55%). In the cortex, there was more newly synthesized [3H]dopamine than [3H]NE, but LC stimulation preferentially increased the synthesis of [3H]NE. The hippocampus contained negligible amounts of [3H]dopamine and was used in subsequent studies. Tyrosine hydroxylase activity was assayed in vitro in supernatants derived from stimulated and control hippocampi. Ten minutes of LC stimulation (20 Hz) maximally activated hippocampal tyrosine hydroxylase and this activation was maintained for up to 20 min after stimulation was terminated. The results illustrate a stimulation-induced activation of NE biosynthesis and tyrosine hydroxylase activity in central NE neurons in vivo. This activation is maintained in the immediate poststimulation period and is not necessarily due to removal of end product inhibition by NE. 相似文献
992.
Neutrophil (polymorphonuclear leukocyte [PMN]) migration into pulmonary airspaces is a prerequisite for clearance of bacteria commonly found in nosocomial pneumonia. Patients at risk for nosocomial pneumonia often experience endotoxemia, and neutrophil dysfunction is associated with endotoxemia in both humans and animals. Using a rodent model of endotoxemia-associated pneumonia, we characterized the altered kinetics of pulmonary PMN trafficking and addressed the roles of platelets, tumor necrosis factor (TNF), and products of complement activation as potential mediators in the modulation of PMN migratory function. In male Sprague-Dawley rats made endotoxemic with intravenously (i.v.) administered endotoxin (lipopolysaccharide [LPS]), recruitment of PMNs into the lung airspaces in response to intratracheally (i.t.) instilled LPS was inhibited. In animals given IT LPS alone (0.5 mg/rat), numbers of airway PMNs were significantly elevated by 2 h, and immunohistochemical evaluation revealed PMNs in alveolar airspaces, alveolar walls, and in interstitium surrounding large airways. LPS (2 mg/kg i.v.) caused neutropenia and pulmonary PMN sequestration within 15 min of administration. Inhibition of airway PMN accumulation occurred by 30 min and lasted for at least 6 h after i.v. LPS. Factors present or activated after 30 min of endotoxemia were hypothesized to mediate the inhibitory effect of i.v. LPS. We found that pretreatment of rats with cobra venom factor to deplete complement (and C5a production) or immunodepletion of platelets or TNF did not affect the ability of i.v. LPS to inhibit pulmonary PMN recruitment or to cause pulmonary leukostasis. In summary, our results show that the inhibitory effects of i.v. LPS on PMN trafficking are rapid and persist for several hours and suggest that neither TNF, C5a, nor platelets are sufficient to mediate the inhibitory response. 相似文献
993.
Christ-Crain M Meier C Roth CB Huber P Staub JJ Müller B 《European journal of clinical investigation》2002,32(12):931-937
BACKGROUND: The estimated prevalence of endogenous subclinical hyperthyroidism varies from 4% to 6% and a basal thyroid stimulating hormone (TSH) level < 0.5 mU L-1 may be associated with increased mortality in subjects over 60 years of age who are not on thyroid medication. Exogenous TSH suppression is a mainstay in the treatment of thyroid cancer. Because of recent concerns about potential adverse effects, especially of endogenous TSH suppression on bone, the cardiovascular system and cognitive functions, subclinical hyperthyroidism obtained new clinical importance. We therefore re-evaluated the diagnostic value of basal and thyrotrop in TRH-stimulated serum TSH measurements using TSH assays with different sensitivities. MATERIALS AND METHODS: A total of 805 oral and nasal TRH stimulation tests were performed on 409 ambulatory subjects with low basal serum TSH concentrations of less than 0.1 mIU L-1. Basal serum TSH was measured either using a second generation assay (functional sensitivity > 0.03 mIU L-1) or two third generation assays (functional sensitivity 0.01 mIU L-1 and 0.007 mU L-1, respectively). Serum TSH concentration was determined before and 3 h after oral administration of 40 mg of TRH and before and 30 min after nasal administration of 2 mg of TRH. RESULTS: In the oral testing group, the basal TSH levels measured by the different TSH assays were 0.06 +/- 0.03, 0.04 +/- 0.02 and 0.03 +/- 0.02, respectively, whereas the peak TSH levels were 0.4 +/- 0.6, 0.4 +/- 0.6 and 0.3 +/- 0.5 in the patients with subclinical hyperthyroidism. In overt hyperthyroidism, the basal TSH levels were 0.06 +/- 0.02, 0.03 +/- 0.02 and 0.03 +/- 0.02, whereas the peak TSH levels were 0.19 +/- 0.3, 0.16 +/- 0.3 and 0.15 +/- 0.2, respectively. Basal TSH values could discriminate between different degrees of TSH suppression if measured with a third generation assay (P < 0.001), but not with a second generation assay. There was only a weak correlation between basal TSH and peak TSH when measured by a second generation assay (n = 126; r = 0.3; P < 0.001) in contrast to the strong correlation found using the third generation assays (n = 128; r = 0.7; P < 0.001 and n = 69; r = 0.8; P < 0.001, respectively). CONCLUSIONS: In view of the recent concerns about potential adverse effects in TSH suppression and based on our data, it is mandatory to select a TSH assay with a functional sensitivity of < or = 0.01 mIU L-1 for optimal titration of L-T4 suppressive therapy, especially in patients with thyroid cancer. If, however, only a second generation TSH assay is available, additional TRH testing allows a more careful titration of suppressive thyroxine therapy. 相似文献
994.
Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis 总被引:32,自引:0,他引:32 下载免费PDF全文
Halangk W Lerch MM Brandt-Nedelev B Roth W Ruthenbuerger M Reinheckel T Domschke W Lippert H Peters C Deussing J 《The Journal of clinical investigation》2000,106(6):773-781
Autodigestion of the pancreas by its own prematurely activated digestive proteases is thought to be an important event in the onset of acute pancreatitis. The mechanism responsible for the intrapancreatic activation of digestive zymogens is unknown, but a recent hypothesis predicts that a redistribution of lysosomal cathepsin B (CTSB) into a zymogen-containing subcellular compartment triggers this event. To test this hypothesis, we used CTSB-deficient mice in which the ctsb gene had been deleted by targeted disruption. After induction of experimental secretagogue-induced pancreatitis, the trypsin activity in the pancreas of ctsb(-/-) animals was more than 80% lower than in ctsb(+/+) animals. Pancreatic damage as indicated by serum activities of amylase and lipase, or by the extent of acinar tissue necrosis, was 50% lower in ctsb(-/-) animals. These experiments provide the first conclusive evidence to our knowledge that cathepsin B plays a role in intrapancreatic trypsinogen activation and the onset of acute pancreatitis. 相似文献
995.
Verschraegen I Anckaert E Schiettecatte J Mees M Garrido A Hermsen D Lentjes EG Liebert A Roth HJ Stamminger G Smitz J 《Clinica chimica acta; international journal of clinical chemistry》2007,380(1-2):75-80
BACKGROUND: Measuring plasma adrenocorticotropic hormone (ACTH) is a key step in the differential diagnosis of hypothalamic-pituitary-adrenal disorders. METHODS: The recently developed electrochemiluminescence Elecsys ACTH immunoassay (Roche Diagnostics, Mannheim, Germany) was evaluated at six clinical laboratories on the Modular E170 and/or the Elecsys 2010 (Roche Diagnostics) immunoanalysers. RESULTS: The within-run and between-run imprecision was 相似文献
996.
Continuous therapeutic epinephrine but not norepinephrine prolongs splanchnic IL-6 production in porcine endotoxic shock 总被引:2,自引:0,他引:2
Bergmann M Gornikiewicz A Tamandl D Exner R Roth E Függer R Götzinger P Sautner T 《Shock (Augusta, Ga.)》2003,20(6):575-581
Catecholamines play a central role in the treatment of sepsis-associated hypotension. However, these hormones have also been shown to modulate the lipopolysaccharide (LPS)-induced induction of cytokines such as tumor necrosis factor alpha, interleukin (IL)-10, and IL-6 in vitro and in human endotoxemia. We hypothesized that catecholamines applied therapeutically in septic shock also influence cytokine patterns. We studied the cytokine response in tissues of the splanchnic compartment in a porcine endotoxin shock model up to 4 h. Shock was induced by a short infusion of LPS, and animals were treated either with fluid resuscitation alone or in combination with continuous epinephrine or norepinephrine. Animals, receiving epinephrine therapy, showed a significantly prolonged upregulation of IL-6 mRNA expression at 4 h after LPS application in liver (P = 0.0014), spleen (P < 0.0001), and mesenteric lymph nodes (P = 0.0078) as compared with animals treated with norepinephrine or fluid resuscitation. Serum IL-6 increased over time in all groups. The total concentration of the cytokine (area under the curve) was significantly higher in the epinephrine group as compared with the norepinephrine and fluid resuscitation groups (P = 0.017). The peak of serum tumor necrosis factor alpha at 1 h after LPS application was already significantly reduced by epinephrine, which was only administered at a mean of less than 0.05 microg/kg/min at this time point (P < 0.01). None of the catecholamines had a significant effect on IL-10 serum levels when compared with animals receiving fluid resuscitation alone. Our data suggest that the therapeutic application of epinephrine but not of norepinephrine is associated with a profound effect on the IL-6 response of splanchnic reticuloendothelial tissues. 相似文献
997.
OBJECTIVE: To review relevant literature supporting the use of aspirin, beta-blockers, lipid-lowering agents, and angiotensin-converting enzyme (ACE) inhibitors for the secondary prevention of coronary heart disease (CHD) in an elderly patient population aged >/=65 years.DATA SOURCES: A MEDLINE search (1990-May 2003) was conducted using the key terms coronary heart disease, secondary prevention and elderly.STUDY SELECTION AND DATA EXTRACTION: Primary and tertiary literature relating to the use of aspirin, beta-blockers, lipid-lowering agents, and ACE inhibitors in the elderly were reviewed.DATA SYNTHESIS: CHD is the leading cause of morbidity and mortality in persons >/=65 years of age, and the use of pharmacologic agents has created a considerable opportunity for reducing recurrent events in those with established disease. This, combined with the aging of the US population, is creating an increase in the number of older adults eligible for secondary prevention. In 2002, the American Heart Association issued a scientific statement on the benefits of specific secondary prevention risk factor interventions in older adults. This article reviews pertinent findings from this statement, along with additional data supporting the use of pharmacologic agents for the secondary prevention of CHD in the elderly.CONCLUSIONS: Data suggest that use of aspirin, beta-blockers, lipid-lowering agents, and ACE inhibitors are effective in secondary prevention of CHD in individuals aged >/=65 years. This benefit is similar to, and often greater than, that observed in younger patients. We believe that these agents should be prescribed for all elderly patients without contraindications. Ongoing studies and future clinical trials will more clearly elucidate the benefits of secondary prevention of CHD, particularly in persons >/=75 years of age, to determine the magnitude of benefits that can be achieved in this population. 相似文献
998.
Elevated serum levels of epithelial cell apoptosis-specific cytokeratin 18 neoepitope m30 in critically ill patients 总被引:2,自引:0,他引:2
Roth GA Krenn C Brunner M Moser B Ploder M Spittler A Pelinka L Sautner T Wolner E Boltz-Nitulescu G Ankersmit HJ 《Shock (Augusta, Ga.)》2004,22(3):218-220
Apoptosis of the epithelium is deemed to play a pivotal role in the pathogenesis of sepsis. A neoepitope in cytokeratin 18 (CK18), termed M30 neoantigen, becomes available at an early caspase cleavage event during apoptosis of epithelium-derived cells and is not detectable in vital or necrotic epithelial cells. A monoclonal antibody, M30, specifically recognizes a fragment of CK18 cleaved at Asp396 (M30 neoantigen). We used an enzyme-linked immunosorbent assay (ELISA) to measure M30 antigen levels in the sera of 15 septic patients. Healthy humans and critical ill patients suffering from severe trauma served as controls. Mann-Whitney U test was used to calculate significance, and a P value of <0.01 was considered to be statistically significant. Serum levels of the CK18 neoepitope M30 were significantly increased in septic patients (236.88 +/- 47.4 U/L) versus trauma (97.2 +/- 17.1 U/L) and healthy controls (66.9 +/- 9.2 U/L) (P < 0.01 and P < 0.008, respectively). The increased serum level of the CK18 neoepitope in septic patients indicates a heightened apoptotic turnover in epithelial cells as compared with trauma patients and healthy controls. Interestingly, nonsurviving trauma patients exhibited a significant increase in the M30 neoantigen as compared with survivors and healthy controls (P < 0.003 and P < 0.002, respectively). The detection of CK18 neoepitope M30 in the serum might be a useful marker in tracing apoptotic epithelium in septic patients. 相似文献
999.
1000.