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21.
Bhattacharya S; MacLennan F; Hamilton MP; Templeton A 《Human reproduction (Oxford, England)》1997,12(7):1440-1442
Although the conventional method of pain relief during outpatient oocyte
recovery involves physician-administered drugs, patient- controlled
analgesia (PCA) offers an alternative technique with the potential to give
women more control over peroperative analgesia. We conducted a prospective
randomized study to compare the effect of fentanyl administered either
through a PCA delivery system or by a physician. Thirty-nine women were
randomized to PCA during egg collection while 42 were allocated to receive
intermittent doses administered by a physician. Pain was evaluated by means
of a 100 mm linear analogue scale. The mean (SD) pain score in the PCA
group was 38.5 (19.8) while in the other group it was 46.1 (21.3) (P =
0.1). In the PCA group, 64% of women felt very satisfied with their
analgesia as compared with 57% in the non-PCA group (P = 0.6). Among the
PCA users, 39% of demands were successful. Significantly more fentanyl
(97.5 microg) was used in the PCA group than in the other group (84.6
microg) (P = 0.03). Though intraoperative PCA with fentanyl is an effective
alternative to physician-administered techniques, many women still feel the
need for more analgesia during the procedure.
相似文献
22.
Brain evolution and lifespan regulation: conservation of signal transduction pathways that regulate energy metabolism 总被引:4,自引:0,他引:4
Mattson MP 《Mechanisms of ageing and development》2002,123(8):947-953
Mechanisms for sensing, acquiring, storing and using energy are fundamental to the survival of organisms at all levels of the phylogenetic scale. Single-cell organisms evolved surface receptors that sense an energy source and, via signal transduction pathways that couple the receptors to the cell cytoskeleton move towards the energy source. Mutlicellular organisms evolved under conditions that favored species that developed complex mechanisms for obtaining food, with nervous systems being critical mediators of energy acquisition and regulators of energy metabolism. A conserved signaling system involved in regulating cellular and organismal energy metabolism, and in sensing and responding to energy/food-related environmental signals, involves receptors coupled to the phosphatidylinositol-3-kinase-Akt signaling pathway. Prominent activators of this pathway are insulin, insulin-like growth factors and brain-derived neurotrophic factor (BDNF). Recent studies in diverse organisms including nematodes, flies and rodents have provided evidence that insulin-like signaling in the nervous system can control lifespan, perhaps by modulating stress responses and energy metabolism. Interestingly, the lifespan-extending effect of dietary restriction in rodents is associated with increased BDNF signaling in the brain, and a related increase of peripheral insulin sensitivity, suggesting a mechanism whereby the brain can control lifespan. Thus a prominent evolutionarily conserved function of the nervous system is to regulate food acquisition and energy metabolism, thereby controlling lifespan. 相似文献
23.
We employed a mouse model of ALS, in which overexpression of a familial ALS-linked Cu/Zn-SOD mutation leads to progressive MN loss and a clinical phenotype remarkably similar to that of human ALS patients, to directly test the excitotoxicity hypothesis of ALS. Under basal culture conditions, MNs in mixed spinal cord cultures from the Cu/Zn-SOD mutant mice exhibited enhanced oxyradical production, lipid peroxidation, increased intracellular calcium levels, decreased intramitochondrial calcium levels, and mitochondrial dysfunction. MNs from the Cu/Zn-SOD mutant mice exhibited greatly increased vulnerability to glutamate toxicity mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors. The increased vulnerability of MNs from Cu/Zn-SOD mutant mice to glutamate toxicity was associated with enhanced oxyradical production, sustained elevations of intracellular calcium levels, and mitochondrial dysfunction. Pretreatment of cultures with vitamin E, nitric oxide-suppressing agents, peroxynitrite scavengers, and estrogen protected MNs from Cu/Zn-SOD mutant mice against excitotoxicity. Excitotoxin-induced degeneration of spinal cord MNs in adult mice was more extensive in Cu/Zn-SOD mutant mice than in wild-type mice. The mitochondrial dysfunction associated with Cu/Zn-SOD mutations may play an important role in disturbing calcium homeostasis and increasing oxyradical production, thereby increasing the vulnerability of MNs to excitotoxicity. 相似文献
24.
25.
Mark P. Mattson M. G. Engle B. Rychlik 《Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid》1991,15(2):117-142
Considerable evidence suggests that altered neuronal calcium homeostasis plays a role in the neuronal degeneration that occurs in an array of neurological disorders. A reduction in microtubules, the accumulation of 8–15 nm straight filaments, and altered antigenicity toward antibodies to the microtubule-associated protein tau and ubiquitin, as well as granulovacuolar degeneration, are observed in many human neurodegenerative disorders. Progress toward understanding how and why human neurons degenerate has been hindered by the inability to examine living human neurons under controlled conditions. We used cultured human fetal cerebral cortical neurons to examine ultrastructural and antigenic changes resulting from elevations in intracellular calcium levels. Elevation of intracellular calcium by exposure to a calcium ionophore or a reduced level of extracellular Na+ for periods of hours to days caused a loss of microtubules, an increase in 8–15 nm straight filaments, and increased immunostaining with Alz-50 and 5E2 (tau antibodies) and ubiquitin antibodies. Granulovacuolar degeneration was also observed. Antigenic changes in tau were sensitive to phosphatases, and the electrophoretic mobility of tau was altered in cells exposed to calcium ionophore, indicating that tau was excessively phosphorylated as the result of elevated intracellular calcium levels. Colchicine also caused an accumulation of straight filaments and altered tau immunoreactivity, suggesting that a disruption of microtubules secondary to altered calcium homeostasis may be a key event leading to altered tau disposition and neuronal degeneration. These data demonstrate that aberrant rises in intraneuronal calcium levels can result in changes in the neuronal cytoskeleton similar to those seen in neurodegenerative disorders, and suggest that this experimental system will be useful in furthering our understanding of the cellular and molecular mechanisms of human neurological disorders. 相似文献
26.
OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation. 相似文献
27.
Iron-overload diseases frequently develop hepatocellular carcinoma. The
genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might
involve an oxidative process via the intermediate production of reactive
oxygen species. This was presently investigated by examining kinetics of
formation and repair of DNA base lesions in primary rat hepatocyte cultures
supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and
100 microM). Seven DNA base oxidation products have been identified in DNA
extracts by gas chromatography- mass spectrometry, which showed a
predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine,
2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil,
5-OH-cytosine) in control cultures. All these DNA oxidation products
revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA
supplementation, among which fapy-adenine showed the highest increase and
5-OH-cytosine was the least prominent. Involvement of iron in this
oxidative process was established by a correlation between extent in DNA
oxidation and intracellular level of toxic low molecular weight iron. DNA
excision- repair activity was estimated by release of DNA oxidation
products in culture medium. All the seven DNA oxidation products were
detected in the medium of control cultures and showed basal repair
activity. This DNA repair activity was increased in a time- and
dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was
5-OHMe-Uracil, were preferentially repaired, which explains the low levels
detected in oxidized DNA. Since oxidized bases substantially differed from
one another in terms of excision rates from cellular DNA, specific
excision- repair enzymes might be involved. Our findings, however,
demonstrate that even though DNA repair pathways were activated in
iron-loaded hepatocyte cultures, these processes were not stimulated enough
to prevent an accumulation of highly mutagenic DNA oxidative products in
genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in
understanding the hepatocarcinogenic evolution of iron-overload diseases.
相似文献
28.
Basic fibroblast growth factor (bFGF) enhances functional recovery following severe spinal cord injury to the rat 总被引:8,自引:0,他引:8
Rabchevsky AG Fugaccia I Turner AF Blades DA Mattson MP Scheff SW 《Experimental neurology》2000,164(2):280-291
We have recently demonstrated that following a moderate contusion spinal cord injury (SCI) to rats, subsequent administration of basic fibroblast growth factor (bFGF) significantly enhances functional recovery and tissue sparing. To further characterize the effects of bFGF, we evaluated its efficacy after a more severe contusion injury at T(10) using the NYU impactor. Immediately after SCI, osmotic minipumps were implanted into the lateral ventricle and lumbar thecal sac to deliver bFGF at 3 or 6 microg per day versus control vehicle for 1 week. Animals were behaviorally tested for 6 weeks before histological assessment of tissue sparing through the injured segment and glial reactivity distal to the lesion. Compared to moderate SCI, all rats had more prolonged and sustained functional deficits 6 weeks after severe contusion. Subjects treated with bFGF had pronounced recovery of hindlimb movements from 2 to 6 weeks compared to controls, manifested in significantly higher behavioral scores. Only marginal tissue sparing was seen rostral to the injury in bFGF-treated spinal cords versus controls. Optical density measurements of astrocyte and microglial cell immunoreactivity in bFGF-treated spinal cords showed that after 6 weeks they approximated controls, although astrocyte immunoreactivity remained higher in controls rostrally. In summary, intrathecal infusion of bFGF following severe SCI significantly restores gross hindlimb motor function that is not correlated with significant tissue sparing. In light of previous evidence that pharmacological intervention with bFGF after moderate SCI enhances tissue preservation, the current findings indicate that yet undefined mechanisms contribute to the enhanced functional recovery following bFGF treatment. 相似文献
29.
Protein kinase C iota protects neural cells against apoptosis induced by amyloid beta-peptide 总被引:5,自引:0,他引:5
Xie J Guo Q Zhu H Wooten MW Mattson MP 《Brain research. Molecular brain research》2000,82(1-2):107-113
Protein kinase C (PKC) isoforms are increasingly recognized as playing important roles in the regulation of neuronal plasticity and survival. Recent findings from studies of non-neuronal cells suggest that atypical isoforms of PKC can modulate apoptosis in various paradigms. Because increasing data support a role for neuronal apoptosis in the pathogenesis of Alzheimer's disease (AD), we tested the hypothesis that PKCiota (PKCiota) can modify vulnerability of neural cells to apoptosis induced by amyloid beta-peptide (ABP), a cytotoxic peptide linked to neuronal degeneration in AD. Overexpression of PKCiota increased the resistance of PC12 cells to apoptosis induced by ABP. Associated with the increased resistance to apoptosis were improved mitochondrial function and reduced activity of caspases. In addition, ABP-induced increases in levels of oxidative stress and intracellular calcium levels were attenuated in cells overexpressing PKCiota. These findings suggest that PKCiota prevents apoptosis induced by ABP by interrupting the cell death process at a very early step, thereby allowing the cells to maintain ion homeostasis and mitochondrial function. 相似文献
30.
Benjamin R. Kipp PhD CT MP Fabiola Medeiros MD Michael B. Campion BS Tammy J. Distad CT Lisa M. Peterson CLSp Gary L. Keeney MD Kevin C. Halling MD PhD Amy C. Clayton MD 《Cancer cytopathology》2008,114(4):228-235