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71.
KM Mair E Robinson KA Kane S Pyne RR Brett NJ Pyne S Kennedy 《British journal of pharmacology》2010,161(1):176-192
Background and purpose:
This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats.Experimental approach:
Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg·kg−1 of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg·kg−1 oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI.Results:
A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT=LT0/(1 +MED). LT0 is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 µg·mL−1.Conclusions:
The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics. 相似文献72.
Hypersensitivity pneumonitis: evaluation with CT 总被引:4,自引:0,他引:4
Thirteen chest radiographs and computed tomographic (CT) scans obtained from 11 patients with hypersensitivity pneumonitis were reviewed. The CT findings were correlated with open lung biopsy findings in seven patients. The two patients with acute hypersensitivity pneumonitis showed air-space opacification on CT scans. An open lung biopsy, done in one of these patients, demonstrated noncaseating granulomas and filling of the air spaces with macrophages. The nine patients with subacute hypersensitivity pneumonitis showed small, rounded opacities and patchy air-space opacification on CT scans. These findings reflected the histologic findings, which consisted of interstitial pneumonitis, cellular bronchiolitis, and small, noncaseating granulomas. The six patients with symptoms for 12 months or longer also showed irregular linear opacities on CT scans, corresponding to areas of fibrosis. CT scans were superior to radiographs in helping to assess the type and extent of abnormalities, and high-resolution CT scans were superior to conventional CT scans. 相似文献
73.
74.
M. MICHAELA OTT ANITA HELBING GERMAN OTT JIRI BARTEK LARS FISCHER ALEXANDER DÜRR HANS KREIPE HANS K. MÜLLER-HERMELINK 《The Journal of pathology》1996,179(3):238-242
Centrocytic lymphoma, or mantle cell lymphoma (MCL), is characterized by a chromosomal translocation t(11;14) (q13;q32) involving the bcl-1 locus on chromosome 11. Cyclin D1 is a cell-cycle regulatory protein essential for G1–S transition and has been identified as a potential transforming gene affected by the translocation. In this study, 32 cases of MCL were analysed for the bcl-1 rearrangement and cyclin D1 protein expression. In 17 cases, a rearrangement at the major translocation cluster of bcl-1 could be detected. Twenty-four cases exhibited nuclear cyclin D1 expression that was not detectable in other B-cell lymphomas ( n =40) or in normal B-cells. In nine MCL samples, cyclin D1 was expressed without a detectable bcl-1 rearrangement. The detection of a t(11;14) by means of classical cytogenetics in one of these cases, however, may suggest that this discrepancy could be due to chromosomal breakages outside the typical translocation cluster region. In two cases, a bcl-1 rearrangement was not accompanied by cyclin D1 expression. This study provides further evidence that cyclin D1 is involved in the pathogenesis of MCL and can be exploited as a diagnostic marker in the differential diagnosis of B-cell lymphomas and in the identification of MCL. 相似文献
75.
Henry G Williamson D Tampi RR 《American journal of Alzheimer's disease and other dementias》2011,26(3):169-183
The objective of this review is to summarize the current data on the use of antidepressants in the treatment of behavioral and psychological symptoms of dementia (BPSD) and to determine whether these medications can be recommended for routine clinical use. A literature search of six major databases (PubMed, Medline, PsychINFO, Scopus, Web of Science and Cochrane collaboration) trials, 8 using a selective serotonin reuptake inhibitor (SSRI) compound and 3 using trazodone showed benefit in the treatment of BPSD. The antidepressant drug was well tolerated in at least 14 of the 19 trials with information about tolerability in one trial not provided in the study (paroxetine or placebo for FTD). This review indicates that antidepressants can be an effective in the treatment of BPSD and are generally well tolerated in elderly demented patients. 相似文献
76.
Mittal V Kurup L Williamson D Muralee S Tampi RR 《American journal of Alzheimer's disease and other dementias》2011,26(1):10-28
Behavioral and Psychological Symptoms of Dementia (BPSD) are increasingly recognized as a major risk factor for caregiver burden, institutionalization, greater impairment in activities of daily living (ADLs), more rapid cognitive decline, and a poorer quality of life. BPSD contribute significantly to the direct and indirect costs of caring for patients with dementia even after adjusting for the severity of cognitive impairment and other co-morbidities. Research on these symptoms has indicated a complex interplay between the biological, psychological and social factors involved in the disease process. Although some psychotropic medications have shown modest efficacy in the treatment of these behaviors, their use has generated controversy due to increasing recognition of the side effects of these medications especially the antipsychotic medications. In this review, we examine the risk of cerebrovascular adverse events (CVAEs) and death with antipsychotic medications when used to treat elderly patients with dementia. 相似文献
77.
Background
Nasopharyngeal carcinoma (NPC) and other head and neck cancer (HNCA) types show a great epidemiological variation in different regions of the world. NPC has multifactorial etiology and many interacting risk factors are involved in NPC development mainly Epstein Barr virus (EBV). There is a need to scrutinize the complicated network of risk factors affecting NPC and how far they are different from that of other HNCA types.Methods
122 HNCA patients and 100 control subjects were studied in the region of the Middle East. Three types of HNCA were involved in our study, NPC, carcinoma of larynx (CL), and hypopharyngeal carcinoma (HPC). The risk factors studied were the level of EBV serum IgG and IgA antibodies measured by ELISA, age, sex, smoking, alcohol intake, histology, and family history of the disease.Results
EBV serum level of IgG and IgA antibodies was higher in NPC than CL, HPC, and control groups (p < 0.01). NPC was associated with lymphoepithelioma (LE) tumors, males, regular alcohol intake, and regular smoking while CL and HPC were not (p < 0.05). CL and HPC were associated with SCC tumors (p < 0.05). Furthermore, NPC, unlike CL and HPC groups, was not affected by the positive family history of HNCA (p > 0.05). The serum levels of EBV IgG and IgA antibodies were higher in LE tumors, regular smokers, younger patients, and negative family history groups of NPC patients than SCC tumors, non-regular smokers, older patients and positive family history groups respectively (p < 0.05) while this was not found in the regular alcoholics (p > 0.05).Conclusion
It was concluded that risk factors of NPC deviate much from that of other HNCA. EBV, smoking, alcohol intake, LE tumors, male patient, and age > 54 years were hot risk factors of NPC while SCC and positive family history of the disease were not. Earlier incidence, smoking, LE tumors, and negative family history of the disease in NPC patients were associated much clearly with EBV. It is proposed that determining the correct risk factors of NPC is vital in assigning the correct risk groups of NPC which helps the early detection and screening of NPC. 相似文献78.
79.
80.
Enio R Vasques Estela RR Figueira Joel A Rocha-Filho Cinthia Lanchotte Jorge LS Ximenes Helena B Nader Ivarne LS Tersariol Marcelo A Lima Tiago Rodrigues José EM Cunha Eleazar Chaib Luiz AC D'Albuquerque Flávio HF Galv?o 《Hepatobiliary & pancreatic diseases international : HBPD INT》2022,21(2):190-192
<正>To the Editor:Ischemia-reperfusion injury following surgery and transplantation can lead to irreversible multiorgan failure.Intracellular calcium overload is associated to cellular death during ischemiareperfusion.A recently discovered heparin fragment (HF),trisulfated disaccharide (TD),that acts on sodium-calcium exchanger(NCX) decreasing intracellular Ca2+,showed effectiveness on protecting hepatocytes from ischemia-reperfusion injury [1], 相似文献