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41.
Evidence indicates that very late stent thrombosis (> 1 year) occurs more frequently in drug-eluting stents than in bare metal stents after discontinuation of clopidogrel. We present a case of an 83 year old man with an LAD in-stent thrombosis 41 months after stenting with a sirolimus-eluting stent in whom clopidogrel was discontinued after 6 months based on these days' guidelines. In-stent thrombus was aspirated and intracoronary ultrasound (ICUS) showed significant in-stent restenosis which had narrowed the minimal lumen diameter by 1 mm. The lesion was stented with a bare metal stent. The patient was discharged after recovery and had no recurrence of stent thrombosis in one month follow-up. We recommended indefinite dual antiplatelet therapy with aspirin and clopidogrel.  相似文献   
42.

Background

Recent researches in the field of genetics have extended our knowledge through the discovery of genetic factors associated with autoimmune diseases (AID). Genetics by itself, however, cannot elucidate all the uncertainties encountered in the etiopathology of AID. On the other hand, incomplete harmony in the prevalence of AID in identical twins suggests that non-genetic factors may play an important role in determining the disease susceptibility. Besides, epigenetics, which is defined by changes in gene expression without a corresponding change in the DNA sequences, has come in to provide new awareness in the disease etiopathology by bridging the genetic and epigenetic factors. The recent advances in the field of epigenetics provide a new insight into the understanding of the disease mechanisms, development, diagnostic and prognostic approaches, as well as the various treatment methods.

Purpose

This review paper aims to present an overview of epigenetic modifications involved in the pathogenesis of systemic lupus erythematosus (SLE) and discuss their important roles in clinical and pharmacological settings, including novel and recent therapeutic applications.

Results

Nowadays, it is believed that autoimmune diseases, such as SLE, begin when genetically susceptible factors associate with environmental triggers. The current therapeutic approaches for SLE treatment have been based on treatments with immunosuppressive drugs, which are linked to various side effects. It is difficult to develop highly effective treatments for SLE patients with minimal or no side effects, mainly due to the disease complexity. The breakthrough of pharmacoepigenetics provides a new approach to solve this problem. Epigenetic modifications can influence the efficacy of drugs by changing the gene expression through modifying chromatin remodeling. In this regard, epigenetic studies in SLE are expected to reveal novel disease biomarkers and therapeutic targets.

Conclusions

Accumulating evidence disclosed that epigenetic dysregulations are engaged in SLE pathogenesis and may be exerted as biomarkers to diagnose and as tools to treat these patients.
  相似文献   
43.
While significant racial disparities in graft outcome persist among adult and pediatric kidney transplant recipients in the US, some international studies do not show these differences. The aim of this study is to examine predictors of graft outcomes and the impact of race in our pediatric kidney transplant cohort. Records of 109 pediatric kidney transplant recipients performed at our institution between 7/99 and 4/07 were studied. Patients were grouped based on race: African-American (AA) vs. non-AA. Fifty-five AA (12 ± 5 years) and 54 non-AA patients (11 ± 6 years) were studied. There were more females, pre-emptive transplants and living donors in the non-AAs. Survival analysis showed significantly higher rejection rates in AAs, P = 0.02, and lower unadjusted graft survival (P = 0.09). Cox Proportional Hazards Survival Regression Analysis revealed biopsy-proven acute rejection and delayed graft function contributed to worse graft survival, while pre-emptive transplantation had a favorable effect. Race was not an independent risk factor for decreased graft survival in the final model. In conclusion, our cohort showed several modifiable risk factors that can partially account for poorer graft survival in pediatric AA kidney transplant recipients.  相似文献   
44.
Antioxidant activity, colour and some nutritional properties of hot air and freeze-dried strawberry tree (Arbutus unedo L.) fruits were investigated. Additionally, the effects of two pre-treatments, namely ethyl oleate and water blanching, were compared in terms of drying characteristics. For determination of antioxidant activities in ethanol extracts, two different analytical methods were used: 1,1-diphenyl-2-picrylhydrazyl scavenging activity and β-carotene bleaching activity. As a result, the ethyl oleate pre-treatment shortened the drying time by hot air method and gave a higher 1,1-diphenyl-2-picrylhydrazyl scavenging activity (82.16?±?0.34%), total phenolic content (7.62?±?1.09?μg GAE/g extract), ascorbic acid content (236.93?±?20.14?mg/100?g), besides hydromethylfurfural was not observed. Freeze-dried fruits exhibited higher ascorbic acid content (368.63?±?17.16?mg/100?g) than those fresh fruits (231.33?±?19.51?mg/100?g) and nearly 1,1-diphenyl-2-picrylhydrazyl activity (93.52?±?0.41 %) to fresh fruits (94.03?±?1.18%). Colour characteristics, sugar content and mineral contents of fruits were significantly affected by pre-treatments and drying methods (p?相似文献   
45.
Cervical HPV infection should be managed less as a typical STI and more as a strong risk factor predisposing to cervical cancer development. HPV infection is undeniably transmitted predominately through sexual contact.However, the fact that more than 80% of women followed over time will acquire at least one HR-HPV infection reflects the ubiquitous nature of the infection and the ease of transmission. Although the behavioral profiles typically associated with an increased risk for STI (including lifetime partner number, age at first intercourse, and so forth) will certainly lead to an increased risk for HPV detection, there is a high absolute prevalence of HPV even among women who have few lifetime sex partners. It could be argued that to counsel patients for an HPV infection as an STI would be counterproductive, as short of absolute abstinence, the prevention of infection is difficult and treatment options, short of excisional procedures for neoplasia, are limited.The real promise held in this area is the availability of an apparently highly effective prophylactic HPV vaccine, targeting at least HPV 16, 18, 6, and 11[33,34]. This vaccine cocktail, if it achieved 100% coverage, could theoretically prevent 50% to 70% of invasive cervical cancers and most genital warts. Vaccination will be required among women before initiation of sexual contact, presumably among girls 10 to 13 years of age. Many programmatic issues remain regarding the implementation of HPV vaccine programs, including the marketing of the vaccine as STI or cancer prevention,as reviewed in detail by Gravitt and Shah [72]. Even in the era of potentially effective vaccines, screening for cervical cancer is likely to remain a priority in cervical cancer prevention programs for at least several decades. Vaccine trials have proven high short-term efficacy; however, these effects were clearly type-specific and antibody titers gradually decrease postvaccination. It is unclear whether the protection will remain over an individual's lifetime without vaccine booster, and oncogenic HPV infections not targeted by vaccination will continue to contribute to risk for development of cervical intraepithelial neoplasia and cancer. Therefore, although the public health success of HPV vaccination is undoubtedly promising, the role of cervical cancer screening as a secondary prevention effort should not be trivialized. In fact, the nature of screening programs should continue to be reevaluated in the context of effective but limited spectrum vaccines.  相似文献   
46.
We report that endotoxin treatment results in decreased amounts of peroxisomes as well as changes in structure and function of peroxisomal membranes. Peroxisomes isolated from the liver of control and treated animals showed a marked decrease in total protein, but no significant alteration in the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) protein profile. However, the Western blot study of the peroxisomal beta-oxidation enzymes and catalase showed an increase in those enzymes in the peroxisomal peak of normal density in endotoxin-treated rats. Disintegration of peroxisomal membranes by carbonate treatment from endotoxin-treated liver and change in the fluidity of peroxisomal membranes suggests alterations in peroxisomal membrane structure. No such alterations were found in mitochondrial or microsomal membranes of endotoxin-treated livers. The lipid analysis of these organelles showed that the only organelle affected was the peroxisome, with a significant decrease in the phospholipid and cholesterol concentrations. To understand the mechanism of endotoxin-mediated alterations in peroxisomes, we studied the possible role of Kupffer cell secreted soluble factors (tumor necrosis factor alpha [TNF-alpha]) on the peroxisomal structure/function. Inactivation/elimination of Kupffer cells by gadolinium chloride before endotoxin treatment did not normalize the overall peroxisomal protein amount and the lipid composition of isolated peroxisomes. However, the levels of individual protein amount in remaining peroxisomes were normalized. Endotoxin also decreased peroxisomal beta-oxidation, and this was partially restored with gadolinium treatment. These results clearly show that peroxisomes are severely affected by endotoxin treatment and suggest that the damage to this organelle may contribute, at least in part, to endotoxin-induced hepatic cytotoxicity.  相似文献   
47.
Depth-ionization measurements were performed using a thin wall parallel plate chamber in water at nominal electron energies of 6, 9, 12, 15, 18, and 22 MeV for the standard available square field sizes. The characteristic parameters of the central axis depth-dose distributions were derived and compared to corresponding values for other accelerators. Vacuum packed therapy-verification films were used in water to obtain isodose distributions in a plane containing the central axis of the beam. The uniformity index and penumbra of the beams were measured from isodose distributions obtained in planes perpendicular to the beam central axis, at depths of 1/2R85 in water.  相似文献   
48.
Tissues from 12 metastatic tumors of the brain were studied immunohistochemically with an antiserum to a glia-specific protein, astroprotein (glial fibrillary acidic protein, GFAP). Emphasis was laid on demonstrating the tissue architecture of metastatic lesions incorporating brain-derived components (astrocytes and glial fibers). Of 12 samples, 11 manifested a number of irregular indentations at the tumor surface. These indentations, which contained astrocytic elements, extended into the tumor tissue in a tapering fashion. In seven cases, the deeper stromal portions of the tumor also contained astroprotein (GFAP)-positive elements. The presence of this glia-specific protein suggests that the stroma of the tumor tissue may in part be derived from preexisting brain tissue. This peculiar tissue architecture of the tumor supports the hypothesis that some of the blood vessels that are located in the stroma of the tumor tissue are also derived from the brain. These observations may be important in understanding the partial preservation of the blood-brain barrier in metastatic brain tumors and the mode of growth of the metastatic lesion, and in selecting the type of chemotherapy that will be most effective in controlling this central nervous system complication of systemic malignancies.  相似文献   
49.
A 75-year-old white woman, otherwise healthy, developed progressively reduced visual acuity primarily in her left eye over 2 months. A computed tomography scan of the head demonstrated a moderately large, round, circumscribed, benign-appearing suprasellar mass that was enhanced with infusion of contrast medium. At craniotomy, a glioma of the optic chiasm that extended into the left optic nerve was observed.  相似文献   
50.
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