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91.
Johannes Woitzik Elke Lassel Ulf C. Schneider Helmut Schroeck Rudolf Graf 《Experimental neurology》2009,218(1):41-350
Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[14C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g− 1 min− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm3 (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution. 相似文献
92.
PTH has diverse effects on bone metabolism: anabolic when given intermittently, catabolic when given continuously. The cellular
mechanisms underlying the varying target cell response are not clear yet. PTH induces RGS-2, a member of the Regulator of
G-protein Signaling protein family, via cAMP/PKA, and inactivates PKC-mediated signaling. To investigate intracellular signaling
pathways with different PTH concentration-time patterns, we treated UMR 106-01 osteoblast-like cells in a perfusion system.
PTH was administered intermittently (4 min/h, 10−7 M) or continuously at an equivalent cumulative dose (6.6 × 10−9 M). cAMP was measured using radioimmunoassay, mRNA levels using real-time rtPCR and ribonuclease protection assay, and protein
levels using Western immunoblotting. A single PTH pulse transiently increased cAMP levels by 2000% ± 1200%. In contrast to
continuous PTH exposure, cAMP induction remained unchanged with intermittent PTH, ruling out desensitization of the PTH receptor.
In continuously perfused cells, RGS-2 abundance was three to five times higher than in cells intermittently exposed to PTH
for up to 12 h. MKP-1 and -3 were significantly less induced with pulsatile PTH; exposure-mode-dependent differences in MMP-13
and IGFBP-5 were small. Pulsatile but not continuous PTH administration prevents PTHrP receptor desensitization and accumulation
of RGS-2 in osteoblasts, which should preserve PKC-dependent signaling. 相似文献
93.
94.
Jing‐Ping Zhang Limin Zheng Jiang‐Hai Wang Karl‐Eric Magnusson Xin Liu 《Phytotherapy research : PTR》2009,23(6):844-850
Ganoderma sinensis has been used widely in Oriental countries for the prevention and treatment of various diseases including cancer. Previous studies have shown that the lipid extract from Ganoderma exhibits direct cytotoxicity against tumor cells. Here, it is reported that the lipid extract from germinating G. sinensis spores, at lower concentrations that have no direct tumoricidal activity, induce potent antitumor immune responses in human monocytes/macrophages. Upon stimulation with the lipid extract, monocytes/macrophages exhibited markedly increased production of proinflammatory cytokines and surface expression of costimulatory molecules. Conditioned medium from stimulated cells effectively suppressed the growth of tumor cells. Apparently, the lipid extract triggered macrophage activation via a mechanism different from that associated with LPS. Moreover, it was observed that the lipid extract could partially re‐establish the antitumor activity of the immunosuppressive tumor‐associated macrophages. These results indicated that in addition to its direct tumoricidal activity, the lipid extract from G. sinensis spores could exert antitumor activity by stimulating the activation of human monocytes/macrophages. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
95.
Lucio Lucchin Amleto D’Amicis Maria Gabriella Gentile Nino Carlo Battistini Maria Antonia Fusco Augusta Palmo Maurizio Muscaritoli Franco Contaldo Emanuele Cereda 《Mediterranean journal of nutrition and metabolism》2009,2(3):171-179
Aim and methods Nutrition, unhealthy lifestyles and cancer appear to be strictly related, but few authors have analysed the interest in dietary
information of cancer patients and their families. This survey was conducted in the Veneto area (Italy) to investigate the
concern of cancer patients and their family members about diet as a health tool before and after diagnosis of cancer.
Results Seven hundred and four questionnaires were collected: 380 from cancer patients and 324 from family members of cancer subjects.
Breast cancer (BC) was the most frequent disease for patients (61.8%) as well as families (26.5%). Generally, the importance
of having precise diet information after diagnosis is recognised by 40.3% of patients, with significant differences between
the various types of cancer: gastric and colon/rectum cancer (GCC) patients were more concerned than BC women about precise
information concerning a diet to follow immediately after diagnosis (p = 0.000, ODs = 3.10, CI 1.68–5.71) or during treatments (p = 0.001, ODs = 2.67, CI 1.46–4.89). The nutritional information is supplied to patients in 34% of cases and to relatives
in 30.3%, often from non-medical sources. In total healthcare workers (family doctor, oncologist, surgeon, dietician) represented
the exclusive source of dietary information for 24.9% of patients and 22.9% of family members. Diet after diagnosis changes
in 69.1% of GCC patients and in 39.2% of BC women. Relatives, particularly women, report difficulties preparing patients’
meals in 30.7% of cases, changes in the eating habits of the entire family in 29.9% and discontent connected with patients
diet in 13.9%. The concern about proper nutrition after diagnosis increases more in GCC subjects (p < 0.025) when compared to BC subjects and in patients with more recent diagnosis (p < 0.041) when compared with patients with diagnosis >5 years ago, while in family members the interest in diet after diagnosis
increases more in women than in men (p < 0.030) without other differences regarding the degree of relationship, type of cancer or diagnosis time. Relatives (92.7%)
have more interest in nutritional education than patients (74.9%). Cancer patients <65 years were more interested in educational
initiatives concerning nutrition (p = 0.000, ODs = 4.46, CI 2.6–7.4) than older patients (>65 years) and female subjects were more concerned than male patients
(p = 0.008, ODs = 2.11, CI 1.2–3.6).
Conclusions The interest in the dietary knowledge and in educational initiatives concerning nutrition is high in cancer patients and their
relatives, although it decreases with the age. The poor attention paid to nutrition of cancer patients by various healthcare
workers deserves consideration, since the psychophysical wellbeing and perhaps also survival of cancer patients can be improved
by correct dietary management, as well as, naturally, by the principal treatments themselves. 相似文献
96.
Michael Kendler Wolfgang Uter reas Rueffer Raffael Shimshoni Eckehardt Jecht 《Pediatric allergy and immunology》2006,17(2):141-147
Atopic eczema/dermatitis syndrome (AEDS) commonly often arises during early infancy. In several intervention studies a beneficial influence on AEDS course of certain intestinal bacteria, administered as 'probiotics', has been described. To evaluate the possible role of the natural intestinal microflora in children with allergic eczema/dermatitis syndrome regarding immediate type hypersensitivity to food allergens, children with food allergy (AAEDS, n = 68) have been compared with children without detectable food allergy (NAEDS, n = 25). All children (n = 93) in preschool age, mean age of 2.6 (+/-1.8) years, diagnosed with AEDS who were treated as inpatients in 2003 in a dermatological hospital were included. The correlation between fecal microflora, parasites and specific immunoglobulin E (IgE) antibodies against common food allergens was analyzed. A similar composition of intestinal microflora in children with AAEDS and NAAEDS was found. The food allergens that were most frequently detected were egg white, cow milk, casein, peanut and hazelnut. Furthermore, a significant association between IgE sensitization against important food allergens and components of the fecal microflora could not be demonstrated. With aging changes occur in the intestinal microbiota [Proteus/Klebsiella and age (rho = -0.607) and Enterococcus and age (rho = -0.428)]. In two subjects of the AAEDS group Blastocystis hominis was found. The composition of natural intestinal microflora in children with AAEDS and NAAEDS was similar. Hence, there is no evidence of a role of the intestinal microflora with regard to the development of infant (food) allergy in children with AEDS. The possible consequences for allergic diseases later in life require further investigation. 相似文献
97.
To overcome specific absorption rate (SAR) limitations of spin-echo-based MR imaging techniques, especially at (ultra) high fields, rapid acquisition relaxation enhancement/TSE (turbo spin echo)/fast spin echo sequences in combination with constant or variable low flip angles such as hyperechoes and TRAPS (hyperTSE) have been introduced. Due to the multiple spin echo and stimulated echo pathways involved in the signal formation, the contrast behavior of such sequences depends on both T2 and T1 relaxation times. In this work, constant and various variable flip angle sequences were analyzed in a volunteer study. It is demonstrated that a single effective echo time parameter TE(eff) can be calculated that accurately describes the overall T2 weighted image contrast. TE(eff) can be determined by means of the extended phase graph concept and is practically independent of field strength. Using the described formalism, the contrast of any TSE sequence can be predicted. HyperTSE sequences are demonstrated to show a robust and well-defined T2 contrast allowing clinical routine MRI to be performed with SAR reductions of typically at least 70%. 相似文献
98.
T. Saarne L. Kaiser H. Grönlund O. Rasool G. Gafvelin M. van Hage-Hamsten 《Clinical and experimental allergy》2005,35(5):657-663
BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients. 相似文献
99.
A. Purohit S. Laffer† C. Metz-Favre A. Verot F. Kricek‡ R. Valenta† G. Pauli 《Clinical and experimental allergy》2005,35(2):186-192
BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity. 相似文献
100.
Skoug John W. Borin Marie T. Fleishaker Joseph C. Cooper Anne M. 《Pharmaceutical research》1991,8(12):1482-1488
The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets. 相似文献