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101.
纳络酮和CPP对大鼠急性脊髓损伤的保护作用 总被引:3,自引:0,他引:3
目的:评价阿片受体拮抗剂纳络酮(NLX)和兴奋性氨基酸受体拮抗剂3-(2-羧基哌嗪-4-基)丙基-1-磷酸(CPP)在脊髓损伤后的治疗效果。方法:以7.5g重物从10cm高处落下致伤大鼠T10脊髓,伤后60min开始治疗,从鞘内给予NLX10mg/kg、CPP100mg/kg、甲基强的松龙(MP)30mg/kg。结果:NLX、CPP、MP均显著促进了脊髓损伤后的神经功能恢复,减少组织损害,NLX、CPP和MP之间无显著差别,但较三者合用的效果为差。结论:脊髓损伤后的继发性损伤是多水平、多因素的综合作用,NLX、CPP与MP联合应用治疗急性脊髓损伤较之单一用药更有效。 相似文献
102.
P. -A. Löschmann K. W. Lange M. Kunow K. -J. Rettig P. Jähnig T. Honoré L. Turski H. Wachtel P. Jenner C. D. Marsden 《Journal of neural transmission (Vienna, Austria : 1996)》1991,3(3):203-213
Summary Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactivity of excitatory glutamatergic projections from the subthalamic nucleus to the output nuclei of the basal ganglia resulting in rigidity and akinesia. In theory pharmacological blockade of these overactive systems should improve parkinsonian symptomatology. The selective AMPA-antagonist NBQX and the competitive NMDA-antagonist CPP are not effective in animal models of Parkinson's disease when given alone but ameliorate parkinsonian symptomatology and stimulate locomotor activity when co-administered with a threshold dose of L-Dopa. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Therefore competitive NMDA and non-NMDA antagonists may offer a new therapeutic strategy for the treatment of Parkinson's disease. 相似文献
103.
Kevin D. Seibert Shanthi Sethuraman Jerry D. Mitchell Kristi L. Griffiths Bernard McGarvey 《Journal of pharmaceutical innovation》2008,3(2):105-112
During the development of a pharmaceutical chemical process, it is vital to establish a control strategy that will ensure
the process performance and fitness for use of the active pharmaceutical ingredient (API), which in turn is essential to the
drug product performance and its fitness for use. As part of the control strategy, it is very important to understand and
establish critical elements of the process, one of which is the establishment of the critical process parameters that impact
the critical quality attributes (CQAs) of the API. In this paper, we are proposing a method for determining the criticality
of a process parameter and whether it should be listed in the common technical document as critical. By using routine process
control capability across a variety of operating conditions and equipment configurations, a risk-based approach is used to
identify parameters that could have a potential of impacting the CQAs of the API. Beyond establishing criticality, and understanding
the operational variability, the knowledge gathered from these approaches can also be used to facilitate the efficient mapping
of a multivariate design space. 相似文献
104.
Hyperventilation in head injury: a review 总被引:10,自引:0,他引:10
The aim of this review was to consider the effects of induced hypocapnia both on systemic physiology and on the physiology of the intracranial system. Hyperventilation lowers intracranial pressure (ICP) by the induction of cerebral vasoconstriction with a subsequent decrease in cerebral blood volume. The downside of hyperventilation, however, is that cerebral vasoconstriction may decrease cerebral blood flow to ischemic levels. Considering the risk-benefit relation, it would appear to be clear that hyperventilation should only be considered in patients with raised ICP, in a tailored way and under specific monitoring. Controversy exists, for instance, on specific indications, timing, depth of hypocapnia, and duration. This review has specific reference to traumatic brain injury, and is based on an extensive evaluation of the literature and on expert opinion. 相似文献
105.
Involvement of tumor suppressor protein p53 and p38 MAPK in caffeic acid phenethyl ester-induced apoptosis of C6 glioma cells 总被引:4,自引:0,他引:4
Caffeic acid phenethyl ester (CAPE), an active component of propolis, has many biological and pharmacological activities including antioxidant, anti-inflammation, antiviral action, and anticancer effect. Our previous studies showed that CAPE exhibited significant cytotoxicity in oral cancer cells. Herein we further investigated the cytotoxicity potential of CAPE and the mechanism of its action in C6 glioma cells. The data exhibited that C6 glioma cells underwent internucleosomal DNA fragmentation 24 hr after the treatment of CAPE (50 microM). The proportion of C6 glioma cells with hypodiploid nuclei was increased to 24% at 36 hr after the exposure. Further results showed that CAPE induced the release of cytochrome c from mitochondria into cytosol, and the activation of CPP32. CAPE application also enhanced the expression of p53, Bax, and Bak. Finally, the potential signaling components underlying CAPE induction of apoptosis were elucidated. We found that CAPE activated extracellular signal-regulated kinase (ERKs) and p38 mitogen-activated protein kinase (p38 MAPK) in C6 glioma cells. More importantly, p38 kinase formed a complex with p53 after the treatment of CAPE for 0.5 hr. The expression of p53, phospho-serine 15 of p53, and Bax, and inactivate form of CPP32 was suppressed by a pretreatment of a specific p38 MAPK inhibitor, SB203580. The resultant data suggest that p38 MAPK mediated the CAPE-induced p53-dependent apoptosis in C6 glioma cells. 相似文献
106.
McCarthy LJ Danielson CF Rothenberger SS Parker C Weidner J Miraglia C Matus D Waxman D 《Transfusion》2000,40(10):1264-1267
BACKGROUND: Three types of plasma are widely available for transfusion. Two plasma components, FFP donor retested (FFP-DR), and solvent/detergent-treated plasma (SDP), are now considered to be safer from infectious complications than FFP. STUDY DESIGN AND METHODS: A large regional blood center attempted to provide FFP-DR exclusively to all its 42 hospitals. Significant planning, increases in computer capabilities, and expansion of component storage areas were completed before initiation of this program. RESULTS: During the first 6 months of the FFP-DR program, the blood center was not able to supply the entire region exclusively with FFP-DR. Consequently, SDP was utilized to supplement the program and to successfully and completely convert the region's 42 hospitals to the use of safer plasma. CONCLUSION: Two new plasma components were utilized to completely convert a blood service region to the use of safer plasma. 相似文献
107.
Cerebral blood flow and metabolism in severe brain injury: the role of pressure autoregulation during cerebral perfusion pressure management 总被引:2,自引:0,他引:2
Mascia L Andrews PJ McKeating EG Souter MJ Merrick MV Piper IR 《Intensive care medicine》2000,26(2):202-205
Objective: To ascertain if norepinephrine can be used as part of the cerebral perfusion pressure (CPP) management to increase arterial blood pressure (MAP) without causing cerebral hyperemia after severe head injury (HI).¶Design: Prospective, interventional study.¶Setting: Intensive care unit in a university hospital.¶Patients: Twelve severely HI patients; median Glasgow Coma Scale was 6 (range 3–8).¶Interventions: CPP management ( = 70 mmHg). Pressure autoregulation (assessed by norepinephrine infusion) was defined intact if %CPP/%CVR ≤ 2.¶Results: Cerebral blood flow (CBF: Xe133 inhalation technique), jugular bulb oxygen saturation (SjO2) and transcranial Doppler (TCD) were recorded during the test. Norepinephrine increased CPP by 33 % ( ± 4). Autoregulation was found to be intact in ten patients and defective in two. In the ten patients with preserved autoregulation, CBF decreased from 31 ± 3 to 28 ± 3 ml/100 g/min; in the two patients with impaired autoregulation CBF increased respectively from 16 to 35 and from 21 to 70 ml/100 g/min. SjO2 did not change significantly from baseline. TCD remained within the normal range.¶Conclusions: During CPP management norepinephrine can be used to increase MAP without potentiating hyperemia if pressure autoregulation is preserved. The assessment of pressure autoregulation should be considered as a guide for arterial pressure-oriented therapy after HI. 相似文献
108.
Previous studies have shown that the N-methyl-D-aspartate (NMDA) receptor is modified during hypoxia in the cerebral cortex of newborn piglets. The present study tests the hypothesis that the NMDA receptor 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) high-affinity binding site is modified during hypoxia and that the degree of modification correlates with the progressive decrease in cerebral cellular energy metabolism and increase in lipid peroxidation induced by hypoxia. Studies were conducted in twelve anesthetized, ventilated newborn piglets, five normoxic and seven hypoxic which were exposed to decreased fraction of inspired oxygen (FiO2) to achieve varying phosphocreatine (PCr) levels. 3[H]-CPP binding was performed with CPP concentrations ranging from 0.5 to 1500 nM at 23 degrees C for 40 min in P2 membrane fractions. Brain tissue PCr levels were determined biochemically. Conjugated dienes (CDs) were measured as an index of lipid peroxidation. In the normoxic group, B(max) (receptor number) for the CPP binding site was 329+/-93 fmol/mg protein and Kd (dissociation constant) 137+/-44 nM, the mean PCr value was 2.5+/-0.4 micromol/g brain and the CD level was 0.0 nmol/g brain. As tissue hypoxia worsened, there was a gradual decline in tissue PCr as well as receptor B(max) and K(d) values, and there was an increase in conjugated dienes. Both the receptor B(max) (r=0.90) and Kd (r=0.72) decreased in a linear relationship as PCr decreased. As the levels of CDs increased both the receptor B(max) (r=0.88) and Kd (r=0.68) decreased in a linear fashion. The data show that there is not a critical hypoxic threshold for modification of the CPP binding site of the NMDA receptor, but that modification is coupled to a gradual decrease in brain cell energy metabolism and increase in lipid peroxidation. We speculate that hypoxia-induced modification of the NMDA receptor is mediated not only by changes in the receptor recognition site but also by an alteration of brain cell membrane structure secondary to conjugated diene formation. 相似文献
109.
P. Van Os-Bossagh L. M. Kosterman W. C. J. Hop B. E. Westerhof J. V. de Bakker A. C. Drogendijk W. A. Van Duyl 《International urogynecology journal》2001,12(2):89-96
The aim of the study was to investigate the occurrence and duration of micromotions of the bladder wall. Thirty women with
CPP and 7 healthy women underwent micromotion detection (MMD). A latex balloon provided with eight electrodes was placed within
the bladder through the urethra and filled with saline up to 200 ml. Micromotions (MM), pressure within the balloon, abdominal
pressure and respiratory excursions of the abdomen were registered simultaneously. A significant difference in duration as
well as frequency of occurrence was found for MM activity between subjects with CPP and controls. For the occurrence of variations
in detrusor presure, the difference between groups tended towards significance. We conclude that there are indications that
the bladder is involved in CPP. 相似文献
110.