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101.
102.
Sexual dimorphism in renal ischemia-reperfusion injury in rats: possible role of endothelin 总被引:4,自引:0,他引:4
Müller V Losonczy G Heemann U Vannay A Fekete A Reusz G Tulassay T Szabó AJ 《Kidney international》2002,62(4):1364-1371
BACKGROUND: Postischemic organ dysfunction is influenced by gender and sexual steroids. METHODS: To compare the susceptibility of the kidney to postischemic failure between sexes, the left vascular pedicle was clamped for 50 minutes in anesthetized male and female Wistar rats. Survival rate, renal and systemic hemodynamics and renal prepro-endothelin (pp-ET) mRNA expression were measured. RESULTS: Eight percent of males as compared to 75% of females survived for more than 7 days. Previous orchidectomy of mature rats or sexual immaturity improved the rate of 7 day survival to 67% and 58%, respectively, as compared to intact males (P < 0.05). Estradiol treatment of mature male animals also resulted in a significantly better survival. Ovariectomy, sexual immaturity or testosterone treatment had no impact on the course of renal failure in females. The early postischemic recovery of renal blood flow was delayed due to a dramatic increase in renal vascular resistance in male versus female rats. The expression of pp-ET gene in the kidneys was increased at 5 minutes following reperfusion and was significantly higher 2 hours after ischemia in males, but not in females. Pretreatment with the endothelin A receptor antagonist LU 135252 provided indistinguishable survival rates in intact male and female rats after warm renal ischemia. CONCLUSION: Female rats enjoy relative protection against postischemic renal failure. Furthermore, in intact males the effects of androgens upon ischemic kidney damage seem to be mediated by endothelin-induced vascular changes. 相似文献
103.
Ahluwalia N de Silva A Atukorala S Weaver V Molls R 《The American journal of clinical nutrition》2002,75(2):289-294
BACKGROUND: Assessing iron status continues to be challenging in field situations. Spot methods developed for analyzing ferritin from serum or plasma samples that are spotted and dried on filter paper have been shown to provide reliable and accurate iron-status assessments. However, the spot methods are based on samples from venous serum or plasma and have not been evaluated in field settings. OBJECTIVE: We evaluated the validity of analyzing ferritin to assess iron status by using venous and capillary dried-serum-spot (DSS) samples by the spot method compared with using serum ferritin by the traditional method in a field setting. DESIGN: Venous and capillary blood was obtained from healthy schoolchildren (n = 100; +/- SD age: 8.9 +/- 0.3 y) in Colombo, Sri Lanka. To prepare DSS samples, we aliquoted precisely 20 microL serum per spot on filter paper, air-dried the spots, and placed them in airtight plastic bags until analysis by the spot ferritin method with the use of cellulase from Trichoderma reesei at 2 wk after collection. Venous serum (100 microL) was frozen until ferritin determination by traditional radioimmunoassay. RESULTS: Venous and capillary DSS ferritin values correlated strongly with traditional serum ferritin values (r = 0.88 and 0.86, respectively; P = 0.0001). The geometric means (+/- 1 SD) for venous and capillary DSS ferritin and traditional ferritin were 26.9 (15.3-47.4), 33.9 (20.9-54.8), and 33.1 (18.6-58.8) microg/L, respectively, and were not significantly different. Venous and capillary DSS methods on average (+/- SD) yielded ferritin values that were 5.8 +/- 10.1 microg/L lower and 0.1 +/- 9.4 microg/L higher, respectively, than serum ferritin values obtained with the traditional method. CONCLUSIONS: Capillary and venous DSS methods for analyzing ferritin provide accurate tools for assessing iron status. Furthermore, capillary DSS ferritin is a practical means of detecting iron deficiency in field settings. 相似文献
104.
Hypericum perforatum L. (St. John’s wort) is one of the leading psychotherapeutic phytomedicines and, because of this, great effort has been devoted to clarifying its mechanism of action. Chronic effects of St. John’s wort and hypericin, one of its major active compounds, on regional brain amine metabolism have not been reported yet. We used a high-performance liquid chromatography system to examine the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine, Hypericum extract or hypericin on regional levels of serotonin (5-HT), norepinephrine, dopamine and their metabolites in the rat brain. We focused our interest on the hypothalamus and hippocampus, as these brain regions are thought to be involved in antidepressant drug action. Imipramine (15 mg/kg, p.o.), Hypericum extract (500 mg/kg, p.o.), and hypericin (0.2 mg/kg, p.o.) given daily for 8 weeks significantly increased 5-HT levels in the hypothalamus (P<0.05). The 5-HT turnover was significantly lowered in both brain regions after 8 weeks of daily treatment with the Hypericum extract (both P<0.05). Consistent changes in catecholamine levels were only detected in hypothalamic tissues after long-term treatment. Comparable to imipramine, Hypericum extract as well as hypericin significantly decreased 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the hypothalamus (P<0.01). Our data clearly show that long-term, but not short-term administration of St. John’s wort and its active constituent hypericin modify levels of neurotransmitters in brain regions involved in the pathophysiology of depression. 相似文献
105.
David R. Edelstein Sanford E. Avner James M. Chow Roger L. Duerksen Jonas Johnson Max Ronis Leonard P. Rybak Warren C. Bierman Brian L. Matthews Veronika M. Kohlbrenner 《The Laryngoscope》1993,103(1):33-41
The efficacy and safety of a once-a-day antibiotic in the treatment of sinusitis was studied. Two randomly assigned groups were treated with either once-a-day cefixime, a third generation cephalosporin, or amoxicillin three times a day. One hundred and fourteen patients were evaluated with antral punctures, microbiologic evaluation, and radiographic studies. Cultures revealed 40% gram-negative organisms, 48% gram-positive, and 12% anaerobes. The most common bacteria were Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus and viridans group streptococci. Ninety-four percent of the cefixime group were cured compared with 96% of the amoxicillin group. Staphylococcus resistance was a problem in both groups, necessitating an occasional change to amoxicillin-clavulanate potassium in the amoxicillin group. Once-a-day antibiotics offer the potential for improved compliance in the treatment of sinusitis. Cefixime offers an additional benefit of covering β-lactamase producing strains of bacteria which are increasing in incidence and resistant to many penicillins. 相似文献
106.
Anticancer efficacy of the irreversible EGFr tyrosine kinase inhibitor PD 0169414 against human tumor xenografts 总被引:4,自引:0,他引:4
Vincent PW Bridges AJ Dykes DJ Fry DW Leopold WR Patmore SJ Roberts BJ Rose S Sherwood V Zhou H Elliott WL 《Cancer chemotherapy and pharmacology》2000,45(3):231-238
Purpose: The involvement of the EGF receptor (EGFr) family of receptors in cancers suggests that a selective inhibitor of the tyrosine
kinase activity of the EGFr family could have a therapeutic effect. PD 0169414, an anilinoquinazoline, is a potent irreversible
inhibitor of the EGFr family tyrosine kinase activity with IC50 values of 0.42 nM against the isolated EGF receptor, and 4.7 nM and 22 nM against EGF- and heregulin-mediated receptor phosphorylation in A431 and MDA-MB-453 cells, respectively. Methods and Results: Oral administration of 260 mg/kg per day PD 0169414 for 15 days to animals bearing advanced-stage A431 epidermoid carcinoma
produced a 28.2-day delay in tumor growth and resulted in three complete and three partial tumor regressions in six animals.
Toxicity at this dose level was limited to <6% loss of initial body weight. Doses of 160 and 100 mg/kg per day produced tumor
growth delays of 29.5 and 20.9 days and two and one complete regressions in six animals, respectively. Subcutaneous, intraperitoneal,
and oral routes of administration have also shown in vivo antitumor activity of PD 0169414 in a panel of human tumor xenografts.
Responsive tumor lines include A431 (human epidermoid carcinoma), H125 (NSCL carcinoma), MCF-7 and UISO-BCA1 (human breast
carcinoma), and SK-OV-03 (human ovarian carcinoma). The therapeutic effect ranged from delayed tumor growth (6.4 days delayed
tumor growth for 14 days of treatment) to tumor regressions (32.2 days delayed tumor growth and five partial regressions in
six animals) in these model systems. Conclusion: PD 0169414 is a specific, irreversible inhibitor of EGFr family tyrosine kinases with significant in vivo activity against
a variety of relevant human tumor xenografts.
Received: 19 May 1999 / Accepted: 11 August 1999 相似文献
107.
108.
Hodgkin's lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin's Study Group. 总被引:3,自引:0,他引:3
Andreas Engert Veronika Ballova Heinz Haverkamp Beate Pfistner Andreas Josting Eckhart Dühmke Konrad Müller-Hermelink Volker Diehl 《Journal of clinical oncology》2005,23(22):5052-5060
PURPOSE: With improved prognosis for patients with Hodgkin's lymphoma (HL), interest increasingly focuses on high-risk groups such as elderly patients. We thus performed a retrospective analysis using the German Hodgkin's Study Group (GHSG) database to determine clinical risk factors, course of treatment, and outcome in elderly HL patients in comparison with younger adults. PATIENTS AND METHODS: A total of 4,251 patients included in the GHSG studies HD5 to HD9 were analyzed, of whom 372 (8.8%) were 60 years or older and 3,879 (91.2%) were younger than 60 years. Patient characteristics, treatment results, toxicity, freedom from treatment failure (FFTF), and overall survival (OS) were compared. RESULTS: Elderly patients more often had mixed cellularity subtype, "B" symptoms, elevated erythrocyte sedimentation rate, and poorer performance status. Less frequently observed were nodular sclerosis subtype, large mediastinal mass, and bulky disease. Acute toxicity during chemotherapy was generally higher in elderly patients. This was most obvious for severe infections (grade 3 or 4; 15% v 6%) correlating with more severe leukopenia in elderly patients (grade 4; 38% v 23%). As a result, significantly fewer elderly patients received the intended full chemotherapy dose (75% v 91%). The survival analysis showed a significantly poorer treatment outcome for elderly patients in terms of 5-year OS (65% v 90%), FFTF (60% v 80%), and HL-specific FFTF (73% v 82%). CONCLUSION: Elderly patients have a poorer risk profile compared with younger HL patients and experience more severe treatment-associated toxicity. Higher mortality during treatment as well as lower dose-intensity are the major factors explaining the poorer overall outcome of elderly HL patients. 相似文献
109.
Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells. The beneficial effect of the anti-parkinsonian monoamine oxidase-B inhibitor, R-(-)-deprenyl has been shown in a number of different diseases, such as Parkinson's and Alzheimer's disease, atherosclerosis or tumor formation. The role of the cytoskeleton, the main component of cell adhesion, has been suggested in the development of these diseases. Nevertheless, the effect of the drug on cell adhesion has never been examined. In the present study, the authors studied the effect of R-(-)-deprenyl on cell-cell adhesion of neuronal (PC12, rat phaeochromocytoma) and non-neuronal (NIH3T3, NIH3T3/EGFR, NIH3T3/EGFR-e3B1 mouse embryo fibroblasts, and 5180 mouse sarcoma) cells using cell association assay. R-(-)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell-cell adhesion of PC12 cells, which contain no monoamine oxidase-B, and we observed the same effect in NIH3T3 cells at concentrations lower than those needed for monoamine oxidase-B inhibition. Interestingly, R-(-)-deprenyl increased cell-cell adhesion of tumor cell lines as well. The effect of R-(-)-deprenyl was not reversible during a 24-hour recovery period. At the same time, the monoamine oxidase-B inactive isomer of the drug, S-(+)-deprenyl had no effect on cell-cell adhesion in PC12 and NIH3T3 cells. In this study, the authors described a new, monoamine oxidase-B independent effect of R-(-)-deprenyl on cell-cell adhesion both in neuronal and non neuronal cells. The authors' results with S-(+)-deprenyl suggest that the sterical structure of the drug is an important factor of the observed effect, which is probably a consequence of an irreversible change in the cells. 相似文献
110.
Efficient cross-priming of tumor antigen-specific T cells by dendritic cells sensitized with diverse anti-MICA opsonized tumor cells 总被引:3,自引:0,他引:3
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Groh V Li YQ Cioca D Hunder NN Wang W Riddell SR Yee C Spies T 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(18):6461-6466
Dendritic cells (DCs) have the capacity to prime tumor-specific T cell responses and are considered as potentially effective vaccines for immunotherapy of cancer. Critical parameters in the development of DC vaccines are the source of tumor antigen (TA) and the mode of DC-loading. Whole tumor cells contain complex assortments of TA, which has been exploited to enhance cross-presentation to CD8 T cells by DCs loaded with anti-syndecan mAb-opsonized myeloma cells. This approach may be broadly improved by targeting the MHC class I chain-related protein A (MICA), which is frequently and abundantly expressed on most if not all types of epithelial cancers but not in normal tissues except intestinal mucosa. Loading of DC with anti-MICA mAb-coated breast, melanoma, or ovarian tumor lines or uncultured ovarian cancer cells efficiently promoted TA cross-presentation and priming of multivalent anti-tumor CD8 and CD4 T cell responses. These were of substantially greater breadth and magnitude than those of T cells primed by peptide-pulsed or apoptotic tumor cell-loaded DCs. These results may advance DC vaccine development and provide a platform for adoptive T cell therapy and TA discovery. These results further suggest that antibody targeting of MICA might be applicable to elicit T cell immunity against tumors of diverse tissue origins in cancer patients. 相似文献