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排序方式: 共有1678条查询结果,搜索用时 15 毫秒
1.
Piotr Podolec Grzegorz Kope? Jakub Podolec Piotr Wilko?ek Marek Krochin Pawe? Rubi? Marcin Cwynar Tomasz Grodzicki Krzysztof Zmudka Wies?awa Tracz 《Hypertension research》2007,30(12):1151-1158
The objectives of this study were to determine the relationship between carotid-femoral (cfPWV) and aortic pulse wave velocity (aPWV) and to compare their modulators and association with coronary artery disease (CAD). We studied 107 consecutive patients (68 men) with a mean age of 60.49+/-8.31 years who had stable angina and had been referred for coronary angiography. cfPWV and aPWV were measured simultaneously during cardiac catheterization using the Complior device and aortic pressure waveform recordings, respectively. Based on the presence or absence of significant coronary artery stenosis (CAS) patients were subdivided into a CAS+ or CAS- group. The mean values of cfPWV and aPWV were 10.65+/-2.29 m/s and 8.78+/-2.24 m/s, respectively. They were significantly higher in the CAS+ (n=71) compared with the CAS- (n=36) group and predicted significant CAS independently of cardiovascular risk factors and mean or systolic aortic blood pressure. aPWV and cfPWV were significantly correlated (r=0.70; p<0.001) but the degree of correlation differed significantly (p<0.03) between the CAS+ (r=0.74, p<0.001) and CAS- group (r=0.46, p=0.003). Age and mean aortic blood pressure were independent predictors for aPWV as well as cfPWV. In the receiver operating characteristic (ROC) analysis, aPWV and cfPWV had similar accuracy in identification of significant CAS (AUC [area under the ROC curve]=0.76 and 0.69, respectively; p=0.13). However, neither cfPWV nor aPWV was effective at differentiating the extent of CAD. In conclusion, aPWV and cfPWV are highly correlated parameters with similar determinants and comparable accuracy in predicting significant CAS. The strength of correlation between these two indices differed significantly between subjects with and those without CAS. 相似文献
2.
Summary: The goal of this study was to develop a new model of ischemia-induced seizures in immature rats using injection of vasoconstrictor Endothelin-1 (ET-1) into the brain. ET-1 (10, 20, or 40 pmol) was infused into the left dorsal hippocampus of freely moving Wistar rats 12 (P12) and 25 (P25) days old. Animals were then video/EEG-monitored for 100 min and monitoring was repeated 22 h later. Parameters of electrographic seizures (frequency and mean duration) as well as pattern of their behavioral correlates were evaluated. The pattern of behavioral seizures was used to develop model-specific scoring system. Cresyl violet and Fluoro Jade-B-staining were used to evaluate brain damage. Extension of the lesion was correlated with seizure severity. After ET-1-injection, seizures occurred in 83–100% animals of all age-and-dose groups and persisted for 24 h except P12 rats with 10 pmol. There were no differences in average seizure duration (18–40 s) or seizure frequency (3–7 seizures/100 min) among individual dose-groups. Between the 1st and 2nd observation period, total seizure duration decreased in 71% of P12 and 47% of P25 rats. Electrographic seizure activity was most frequently accompanied by clonus, incidence of more severe convulsions (barrel rolling or generalized clonic seizures) increased with dose of ET-1. Morphologic examination did not reveal any dose-related difference in damage severity, hippocampal damage was however more extensive in P12 compared to P25 animals. Seizure severity correlated positively with severity of the damage in both age groups. Our study presents focal injection of ET-1 into the brain as a new and practical model of ischemia-induced seizures in immature rats. 相似文献
3.
Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease 总被引:2,自引:0,他引:2
Janosíková B Pavlíková M Kocmanová D Vítová A Veselá K Krupková L Kahleová R Krijt J Kraml P Hyánek J Zvárová J Andel M Kozich V 《Molecular genetics and metabolism》2003,79(3):167-175
It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD. 相似文献
4.
Natural mechanisms protecting against cancer 总被引:10,自引:0,他引:10
Carcinogenesis is a multistage process. At each step of this process, there are natural mechanisms protecting against development of cancer. The majority of cancers in humans is induced by carcinogenic factors present in our environment including our food. However, some natural substances present in our diet or synthesized in our cells are able to block, trap or decompose reactive oxygen species (ROS) participating in carcinogenesis. Carcinogens can also be removed from our cells. If DNA damage occurs, it is repaired in most of the cases. Unrepaired DNA alterations can be fixed as mutations in proliferating cells only and mutations of very few strategic genes can induce tumor formation, the most relevant are those activating proto-oncogenes and inactivating tumor suppressor genes. A series of mutations and/or epigenetic changes is required to drive transformation of a normal cell into malignant tumor. The apparently unrestricted growth has to be accompanied by a mechanism preserving telomeres which otherwise shorten with succeeding cell divisions leading to growth arrest. Tumor can not develop beyond the size of 1–2 mm in diameter without the induction of angiogenesis which is regulated by natural inhibitors. To invade the surrounding tissues epithelial tumor cells have to lose some adhesion molecules keeping them attached to each other and to produce enzymes able to dissolve the elements of the basement membrane. On the other hand, acquisition of other adhesion molecules enables interaction of circulating tumor cells with endothelial cells facilitating extravasation and metastasis. One of the last barriers protecting against cancer is the activity of the immune system. Both innate and adaptive immunity participates in anti-tumor effects including the activity of natural killer (NK) cells, natural killer T cells, macrophages, neutrophils and eosinophils, complement, various cytokines, specific antibodies, and specific T cytotoxic cells. Upon activation neutrophils and macrophages are able to kill tumor cells but they can also release ROS, angiogenic and immunosuppressive substances. Many cytokines belonging to different families display anti-tumor activity but their role in natural anti-tumor defense remains largely to be established. 相似文献
5.
Fagoonee S Gburek J Hirsch E Marro S Moestrup SK Laurberg JM Christensen EI Silengo L Altruda F Tolosano E 《The American journal of pathology》2005,166(4):973-983
Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme-iron recovery. We used haptoglobin-null mice to evaluate the impact of haptoglobin gene inactivation on iron metabolism. Haptoglobin deficiency led to increased deposition of hemoglobin in proximal tubules of the kidney instead of the liver and the spleen as occurred in wild-type mice. This difference in organ distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload. 相似文献
6.
This paper continues the systematic review on proanthocyanidins and flavan-3-ols in the prevention and treatment of periodontal disease and covers the immunomodulatory effects, and animal- and clinical studies, while the other part discussed the direct antibacterial properties. Inflammation as a major response of the periodontal tissues attacked by pathogenic microbes can significantly exacerbate the condition. However, the bidirectional activity of phytochemicals that simultaneously inhibit bacterial proliferation and proinflammatory signaling can provide a substantial alleviation of both cause and symptoms. The modulatory effects on various aspects of inflammatory and overall immune response are covered, including confirmed and postulated mechanisms of action, structure activity relationships and molecular targets. Further, the clinical relevance of flavan-3-ols and available outcomes from clinical studies is analyzed and discussed. Among the numerous natural sources of flavan-3-ols and proanthocyanidins the most promising are, similarly to antibacterial properties, constituents of various foods, such as fruits of Vaccinium species, tea leaves, grape seeds, and tannin-rich medicinal herbs. Despite a vast amount of in vitro and cell-based evidence of immunomodulatory there are still only a few animal and clinical studies. Most of the reports, regardless of the used model, indicated the efficiency of these phytochemicals from cranberries and other Vaccinium species and tea extracts (green or black). Other sources such as grape seeds and traditional medicinal plants, were seldom. In conclusion, the potential of flavan-3-ols and their derivatives in prevention and alleviation of periodontal disease is remarkable but clinical evidence is urgently needed for issuing credible dietary recommendation and complementary treatments. 相似文献
7.
Hlávka Jakub P. Yu Jeffrey C. Goldman Dana P. Lakdawalla Darius N. 《The European journal of health economics》2021,22(4):559-569
The European Journal of Health Economics - Pharmaceuticals are priced uniformly by convention, but vary in their degree of effectiveness for different disease indications. As more high-cost... 相似文献
8.
Katarzyna Kozar Rafal Kamiński Tomasz Switaj Tomasz O?dak Eugeniusz Machaj Piotr J Wysocki Andrzej Mackiewicz Witold Lasek Marek Jakóbisiak Jakub Go?ab 《Clinical cancer research》2003,9(8):3124-3133
PURPOSE: Recent findings indicating that many genes related to cancer development are silenced by an aberrant DNA methylation suggest that inhibitors of this process may be effective cancer therapeutics. In this study we investigated the efficacy of low-dose 5-aza-2'-deoxycitydine (DAC), a methylation inhibitor, with interleukin (IL) 12, one of the most potent cytokines with antitumor activity. Experimental Design: Mice inoculated with L1210 leukemia cells or with B16F10 melanoma cells were treated with 7 daily injections of low-dose DAC (0.2 mg/kg) and/or 7 daily doses of IL-12 (100 ng/dose). Scid/scid mice as well as monoclonal antibodies against CD4, CD8, and NK1.1 were used to investigate the mechanisms of the antitumor effects of the combination treatment. The activity of murine lymphocytes was measured with enzyme-linked immunospot and (51)Cr release assays. RESULTS: Treatment with DAC or IL-12 given alone produced moderate antitumor effects. In both tumor models combined treatment resulted in potentiated antitumor effects and produced 70% long-term survivors among mice inoculated with L1210 cells. The antitumor efficacy of combined treatment was abrogated in scid/scid mice, and after depletion of CD4(+) and CD8(+) T cells. Mice inoculated with B16F10 melanoma cells had significantly delayed tumor growth after combined treatment with DAC and IL-12. Strong antitumor effect correlated with a significant activation of lymph node-derived CD8(+) and CD4(+) cells. Transient neutropenia was observed in mice under treatment of DAC alone, but remarkably this effect was not potentiated by IL-12. CONCLUSIONS: This study provides the first evidence that antitumor effects of DAC can be strongly potentiated by IL-12 and could be beneficial in an effective low-dose-based antitumor therapy. 相似文献
9.
Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice. 总被引:2,自引:0,他引:2
Marcin Makowski Tomasz Grzela Justyna Niderla Maciej ?Azarczyk Pawe? Mróz Maciej Kopeé Magdalena Legat Katarzyna Strusińska Katarzyna Koziak Dominika Nowis Piotr Mrówka Maria Wasik Marek Jakóbisiak Jakub Go?ab 《Clinical cancer research》2003,9(14):5417-5422
PURPOSE: The aim of the present study was to potentiate the antitumor effectiveness of photodynamic therapy (PDT). A cDNA microarray analysis was used to evaluate the gene expression pattern after Photofrin-mediated PDT to find more effective combination treatment with PDT and inhibitor(s) of the identified gene product(s) overexpressed in tumor cells. EXPERIMENTAL DESIGN: Atlas Mouse Stress Array was used to compare the expression profile of control and PDT-treated C-26 cells. The microarray results have been confirmed using Western blotting. Cytostatic/cytotoxic in vitro assay as well as in vivo tumor models were used to investigate the antitumor effectiveness of PDT in combination with cyclooxygenase (COX) 2 inhibitors. RESULTS: PDT induced the expression of 5 of 140 stress-related genes. One of these genes encodes for COX-2, an enzyme important in the tumor progression. Inhibition of COX-2 in vitro with NS-398, rofecoxib, or nimesulide, or before PDT with nimesulide did not influence the therapeutic efficacy of the treatment. Administration of a selective COX-2 inhibitor after PDT produced potentiated antitumor effects leading to complete responses in the majority of treated animals. CONCLUSIONS: COX-2 inhibitors do not sensitize tumor cells to PDT-mediated killing. However, these drugs can be used to potentiate the antitumor effectiveness of this treatment regimen when administered after tumor illumination. 相似文献
10.
Wojciech Sawczuk Agnieszka Merkisz-Guranowska Dariusz Ulbrich Jakub Kowalczyk Armando-Miguel Rilo Cas 《Materials》2022,15(18)
This paper presents the results of tests on the railway disc brake with regard to the weight wear of friction pads. The tests were carried out at a certified brake test bench where the friction-mechanical characteristics of the railway brake were determined. The test stand was additionally equipped with a thermal imaging camera to observe the contact between the brake pads and the brake disc. The scientific goal of the test is to evaluate the relationship between the weight wear of friction pads and the quantities characterizing the braking process. The quantities characterizing the braking process included pad-to-disc contact area, friction pad thickness, pad-to-disc pressure, and braking speed. A regression model to estimate the friction pad wear on the basis of a single braking with the given input quantities was determined. The greatest influence on the increase in weight wear of friction pads has the braking velocity, which was confirmed by the value of the correlation coefficient of the regression model at value 0.81. The pressure of the friction pad to the disc and the friction pad thickness do not have a significant effect on the weight wear described by the regression model, and the obtained correlation coefficient for these parameters was lower than the value of 0.2. 相似文献