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21.
G. Lallement Didier Clarençon Catherine Masqueliez Dominique Baubichon Monique Galonnier Marie-France Burckhart Michel Peoc’h Jean Claude Mestries 《Archives of toxicology》1997,72(2):84-92
Organophosphorus nerve agents are still in use today in warfare and as terrorism compounds. Classical emergency treatment
of organophosphate poisoning includes the combined administration of a cholinesterase reactivator (an oxime), a muscarinic
cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). However, recent experiments with
primates have demonstrated that such treatment, even when administered immediately after organophosphate exposure, does not
rapidly restore normal electroencephalographic (EEG) activity and fails to totally prevent neuronal brain damage. The objective
of this study was to evaluate, in a realistic setting, the therapeutic benefit of administration of GK-11 (gacyclidine), an
antiglutamatergic compound, as a complement to the available emergency therapy against organophosphate poisoning. GK-11 was
injected at a dose of 0.1 mg/kg (i.v) after a 45-min latency period to heavily intoxicated (8 LD50) primates. Just after intoxication, man-equivalent doses of one autoinjector containing atropine/pralidoxime/diazepam were
administered. The effects of GK-11 were examined on survival, EEG activity, signs of toxicity, recovery after challenge and
central nervous system histology. The present data demonstrate that treatment with GK-11 prevents the mortality observed after
early administration of classical emergency medication alone. EEG recordings and clinical observations also revealed that
GK-11 prevented soman-induced seizures and motor convulsions. EEG analysis within the classical frequency bands (beta, theta,
alpha, delta) demonstrated that central activity was totally restored to normal after GK-11 treatment, but remained profoundly
altered in animals receiving atropine/pralidoxime/diazepam alone. GK-11 also markedly accelerated clinical recovery of soman-challenged
primates. Lastly, this drug totally prevented the neuropathology observed 3 weeks after soman exposure in animals treated
with classical emergency treatment alone. GK-11 represents a promising adjuvant therapy to the currently available emergency
polymedication to ensure optimal management of organophosphate poisoning in man. This drug is presently being evaluated in
a human clinical trial for a different neuroprotective indication.
Received: 16 June 1997 / Accepted: 23 September 1997 相似文献
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24.
Catherine McDonald 《The Journal of school nursing》2006,22(4):193-200
Self-mutilation is not a new trend or phenomenon in adolescents. Self-mutilation can be divided into three categories: major, stereotypic, and moderate/superficial. Moderate/superficial self-mutilation is the most common type in adolescents and includes cutting, burning, and carving. School nurses are positioned to identify, to assist, and to educate adolescents who are self-mutilating, as well as those who may be at risk. A crucial intervention by school nurses is referral of students who are self-mutilating, because it is a gateway to treatment. Treatment, which includes therapy and medication, may be a difficult and lengthy process. The adolescent who self-mutilates may find the school environment difficult during treatment. School nurses must become educated about adolescent self-mutilation in order to care for those who engage in this behavior. Prevention of self-mutilation should focus on increasing coping mechanisms, facilitating decision-making strategies, encouraging positive relationships, and cultivating self-esteem. 相似文献
25.
Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings 总被引:7,自引:0,他引:7
Catherine M. Vogelweid Gayle C. Johnson Cynthia L. Besch-Williford Joe Basler Sara E. Walker 《Journal of neuroimmunology》1991,35(1-3):89-99
The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain. 相似文献
26.
A. Ian Smith Catherine A. Wallace Lain J. Clarke John W. Funder 《Journal of neuroendocrinology》1989,1(5):357-362
In the sheep, unlike many other species, a significant proportion (>25%) of immunoreactive β-endorphin in the anterior pituitary is post-translationally modified to opioid-inactive, α-N-acetylated forms. In a study to determine the precise molecular nature of α-N-acetylated β-endorphin immunoreactivity, we noted a striking difference in high-performance liquid chromatography profiles of anterior pituitary extracts between sheep killed on the farm, and age-, sex- and strain-matched slaughterhouse animals. These altered patterns of a-N-acetylated β-endorphin processing were reproduced in farm animals by chronic (≤ 4 days) treatment with the synthetic glucocorticoid dexamethasone; in contrast dexamethasone had no effect on a-N-acetylated β-endorphin processing in hypothalamo-pituitary disconnected sheep. These data suggest that (1) the change in processing is a stress response, mediated by prolonged glucocorticoid exposure, (2) this effect is central, rather than a direct effect on the pituitary, and (3) the relative abundance of various peptide sequences in slaughterhouse-derived material may not reflect their abundance under more physiological conditions. 相似文献
27.
Catherine M. Cahill Melissa J. Green Rajeev Jairam Gin S. Malhi 《Early intervention in psychiatry》2007,1(2):138-149
Aim: This article reviews research centred around juvenile bipolar disorder with particular reference to diagnostic difficulties. Putative deficits are scrutinized with respect to trait likelihood and the roles of neuropsychology and neuroimaging in enhancing our understanding of juvenile bipolar disorder are discussed. Methods: Search terms including childhood, adolescent, youth and juvenile combined with the terms ‘bipolar disorder’, mania, depression and hypomania were used to identify relevant studies in MEDLINE and PsychLit. Results: Over recent years research into this relatively new disorder has increased phenomenally. Key issues within the field include diagnostic specificity, the heritability of the disorder, the impact of comorbidity and the implications of neuropsychological and neuroimaging findings. Conclusion: Despite concerning controversies in literature the diagnosis of bipolar disorder in children and adolescents as compared with adults, promising future research directions include better neurological characterization of the disorder through the application of findings from clinical populations, neuropsychological and neuroimaging research. 相似文献
28.
Dympna Harmey Gudrun Stenbeck Catherine D Nobes Alistair J Lax Agamemnon E Grigoriadis 《Journal of bone and mineral research》2004,19(4):661-670
The role of the Rho-Rho kinase signaling pathway on osteoblast differentiation was investigated using primary mouse calvarial cells. The bacterial toxin PMT inhibited, whereas Rho-ROK inhibitors stimulated, osteoblast differentiation and bone nodule formation. These effects correlated with altered BMP-2 and -4 expression. These data show the importance of Rho-ROK signaling in osteoblast differentiation and bone formation. INTRODUCTION: The signal transduction pathways controlling osteoblast differentiation are not well understood. In this study, we used Pasteurella multocida toxin (PMT), a unique bacterial toxin that activates the small GTPase Rho, and specific Rho inhibitors to investigate the role of Rho in osteoblast differentiation and bone formation in vitro. MATERIALS AND METHODS: Primary mouse calvarial osteoblast cultures were used to investigate the effects of recombinant PMT and Rho-Rho kinase (ROK) inhibitors on osteoblast differentiation and bone nodule formation. Osteoblast gene expression was analyzed using Northern blot and RT-PCR, and actin rearrangements were visualized after phalloidin staining and confocal microscopy. RESULTS: PMT stimulated the proliferation of primary mouse calvarial cells and markedly inhibited the differentiation of osteoblast precursors to bone nodules with a concomitant inhibition of osteoblastic marker gene expression. There was no apparent causal relationship between the stimulation of proliferation and inhibition of differentiation. PMT caused cytoskeletal rearrangements because of activation of Rho, and the inhibition of bone nodules was completely reversed by the Rho inhibitor C3 transferase and partly reversed by inhibitors of the Rho effector, ROK. Interestingly, Rho and ROK inhibitors alone potently stimulated osteoblast differentiation, gene expression, and bone nodule formation. Finally, PMT inhibited, whereas ROK inhibitors stimulated, bone morphogenetic protein (BMP)-2 and -4 mRNA expression, providing a possible mechanism for their effects on bone nodule formation. CONCLUSIONS: These results show that PMT inhibits osteoblast differentiation through a mechanism involving the Rho-ROK pathway and that this pathway is an important negative regulator of osteoblast differentiation. Conversely, ROK inhibitors stimulate osteoblast differentiation and may be potentially useful as anabolic agents for bone. 相似文献
29.
Karl Fournier MD ; Catherine Tavera PhD ; Paul Brazeau PhD ; Thierry Abribat DVM PhD 《Wound repair and regeneration》1996,4(2):252-258
Proteases that reduce insulin-like growth factor binding protein-3 affinity for insulin-like growth factor-I have been found in various biological fluids from human beings and rats. The aim of this study was to assess the local and systemic role of insulin-like growth factor binding protein-3 proteases in the course of wound healing. Six rats had polyvinyl alcohol sponges implanted subcutaneously. Wound fluid and serum were collected 3 days after wounding. Gel filtration experiments showed that insulin-like growth factor-I was present as a 150 kDa complex in both serum and wound fluid. However, insulin-like growth factor binding protein-3 measured by Western ligand blotting was virtually absent in wound fluid. Co-incubation of serum and wound fluid resulted in an ethylenediamine tetraacetic acid-inhibitable degradation of serum insulin-like growth factor binding protein-3, suggesting the presence of an insulin-like growth factor binding protein-3 degrading activity in wound fluid. Incubation of ((125)I)-labeled insulin-like growth factor binding protein-3 in wound fluid and serum showed a rapid and time-dependent proteolysis of insulin-like growth factor binding protein-3 in wound fluid with metabolites similar to those generated by human term pregnant serum. No sign of insulin-like growth factor binding protein-3 degrading activity was observed in rat-serum. In conclusion, there is an insulin-like growth factor binding protein-3 proteolytic activity in wound fluid, and it is hypothesized that this activity results in a localized increase in insulin-like growth factor-I bioactivity. 相似文献
30.
Prediction of Remission of Acute Posttraumatic Stress Disorder in Motor Vehicle Accident Victims 总被引:1,自引:0,他引:1
Edward B. Blanchard Edward J. Hickling Catherine A. Forneris Ann E. Taylor Todd C. Buckley Warren R. Loos James Jaccard 《Journal of traumatic stress》1997,10(2):215-234
One hundred forty five individuals who sought medical attention as a result of a motor vehicle accident (MVA), and who were initially assessed 1 to 4 months post-MVA, were followed up prospectively for 6 months to determine how many of the 55 with posttraumatic stress disorder (PTSD) and the 43 with sub-syndromal PTSD would remit and what variables would predict remission. Thirty (55%) of those with initial PTSD had remitted at least in part by 6 months while 67% of those with sub-syndromal PTSD had remitted (and 5% had worsened). Four variables, including severity of initial symptoms, degree of initial physical injury, relative degree of physical recovery by 4 months and whether a close family member suffered a trauma during the follow-up interval, combined to classify 6-month clinical status of 84% of those with initial PTSD secondary to MVAs. 相似文献