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1.
Erythropoietin(EPO) is one of the most successful biopharmaceuticals in history and is used for treating anemia of different origins. However, it became clear that EPO could also work in a neuroprotective, antiapoptotic, antioxidative, angiogenetic and neurotropic way. It causes stimulation of cells to delay cell apoptosis, especially in the central nervous system. In rodent models of focal cerebral ischemia, EPO showed an impressive reduction of infarct size by 30% and improvement of neurobehavioral outcome by nearly 40%. A large animal model dealing with ischemia and reperfusion of the spinal cord showed that EPO could reduce the risk of spinal cord injury significantly. In addition, some clinical studies tested whether EPO works in real live clinical settings. One of the most promising studies showed the innocuousness and improvements in follow-up, outcome scales and in infarct size, of EPO-use in humans suffering from ischemic stroke. Another study ended unfortunately in a negative outcome and an increased overall death rate in the EPO group. The most possible reason was the involvement of patients undergoing simultaneously systemic thrombolysis with recombinant tissue plasminogen activator. An experimental study on rats demonstrated that administration of EPO might exacerbate tissue plasminogen activator-induced brain hemorrhage without reducing the ischemic brain damage. This case shows clearly how useful animal models can be to check negative side effects of a treatment before going into clinical trials. Other groups looked in human trials at the effects of EPO on the outcome after ischemic stroke, relation to circulating endothelial progenitor cells, aneurysmal subarachnoid hemorrhage, traumatic brain injury, hemoglobin transfusion thresholds and elective first-time coronary artery bypass surgery. Most of the results were positive, but are based mostly on small group sizes. However, some of the most neglected facts when focusing on experimental setups of ischemia of the central nervous system are issues like age and comorbidities. It might be extremely worthy to consider these points for future projects, because EPO might influence all these factors. 相似文献
2.
Autoimmune hepatitis type 1 and primary biliary cirrhosis have distinct bone marrow cytokine production 总被引:3,自引:0,他引:3
Zachou K Rigopoulou EI Tsikrikoni A Alexandrakis MG Passam F Kyriakou DS Stathakis NE Dalekos GN 《Journal of autoimmunity》2005,25(4):389-288
We have recently reported differences in the hematopoiesis between autoimmune hepatitis type 1 (AIH-1) and primary biliary cirrhosis (PBC). In view of the notion that cytokines are regulators of hematopoiesis, we investigated in our tertiary center the cytokine production in the bone marrow (BM) of the same consecutive cohort of patients (13 AIH-1, 13 PBC, 10 healthy and 7 patients with cirrhosis due to chronic hepatitis B). Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) were determined in the supernatants of long-term BM cultures by ELISAs. IL-4, TNF-alpha and TGF-beta were found significantly increased in the BM of PBC patients compared to AIH-1 and both control groups. AIH-1 patients had significantly higher BM IL-10 compared to PBC patients and higher IL-10, IL-4 and TNF-alpha compared to controls. BM IFN-gamma was significantly higher in PBC and AIH-1 patients compared to controls. In AIH-1 patients, IL-10 was positively correlated with CD34+, CD34+/CD38- and CD34+/CD38+ cell proportions. In conclusion, the BM cytokine microenvironment of PBC and AIH-1 patients differs significantly compared to that of healthy individuals and cirrhotic patients of non-autoimmune etiology. Differences were also found between patients with PBC and AH-1. The implication of BM in the pathogenesis of autoimmune liver diseases is possible and needs further investigation. 相似文献
3.
Chryssi Foroglou et Georges Winckler 《Anatomy and embryology》1973,140(1):19-37
Summary The ultrastructure of the muscle spindles has been studied in human lumbrical muscles. The findings have been compared with the morphology of muscle spindles of rat and sheep examined with light and electron microscopy. The study is based on cross and longitudinal sections of the entire muscle spindle obtained by dissection. The different components of the spindle are described with special reference to the nuclear bag and nuclear chain fibres. These nuclei have been examined in human adult and newborn material and compared to the animal ones. ADN measurements revealed that although there are morphological differences between the two kinds of nuclei in human newborn spindles, the amount of ADN is the same as well in the nuclear bag as in the nuclear chain nuclei. Special attention is also given to the sensory and motor endings in the muscle spindles and to the presence of Pacinian corpuscules in these receptors. Finally two kinds of leptomeric organelles are described in human material. 相似文献
4.
Nicolaos C. Tassopoulos Krzysztof Krawczynski Angelos Hatzakis Antigoni Katsoulidou Ioanna Delladetsima Maria G. Koutelou Dimitrios Trichopoulos 《Journal of medical virology》1994,42(2):124-128
The aim of this study was to determine the frequency of hepatitis E virus (HEV) infection in a population of Greek adults with community-acquired (sporadic) non-A, non-B hepatitis found to be seronegative for antibodies to hepatitis C virus (anti-HCV). All patients admitted to the Liver Unit of Western Attica General Hospital and diagnosed as having acute community-acquired non-A, non-B hepatitis between February, 1986, and May, 1990, were enrolled in follow up studies (n = 66). Nineteen patients with HCV infection and 11 patients with acute non-A, non-B, non-C hepatitis that progressed to chronicity were excluded. Convalescent sera were tested for antibody to HEV (anti-HEV) by a fluorescent antibody blocking assay in 33 of 36 eligible patients. One of the 33 (3%) patients was found to be positive for anti-HEV. Anti-HEV testing of all 20 available serum specimens from this patient showed evidence of anti-HEV seroconversion at the fourth week after the onset of hepatitis. The patient had not travelled abroad or within Greece or had not had apparent contact with people from foreign countries for the previous 3 months. These data show that HEV infection is not a major cause of community-acquired non-A, non-B hepatitis in Greece. However, the reported case of HEV hepatitis suggests that HEV may retain a low endemicity in Greece. More extensive seroprevalence studies are needed for an accurate estimation of the extent of HEV infection in the southeastern European countries. © 1994 Wiiey-Liss, Inc. 相似文献
5.
A reporting system for endometrial cytology: Cytomorphologic criteria—Implied risk of malignancy 下载免费PDF全文
Niki Margari M.D. Ph.D. Abraham Pouliakis Ph.D. Dionysios Anoinos M.D. Ph.D. Emmanouil Terzakis M.D. Ph.D. Nikolaos Koureas M.D. Charalampos Chrelias M.D. George Marios Makris M.D. Assimakis Pappas M.D. Ph.D. Evripidis Bilirakis M.D. Ph.D. Christina Goudeli M.D. Vasileia Damaskou M.D. Nicolaos Papantoniou M.D. Ioannis Panayiotides M.D. Petros Karakitsos M.D. 《Diagnostic cytopathology》2016,44(11):888-901
6.
Purpose
Three- dimensional (3D) printing has received significant attention as a manufacturing process for pharmaceutical dosage forms. In this study, we used Fusion Deposition Modelling (FDM) in order to print “candy – like” formulations by imitating Starmix® sweets to prepare paediatric medicines with enhanced palatability.Methods
Hot melt extrusion processing (HME) was coupled with FDM to prepare extruded filaments of indomethacin (IND), hypromellose acetate succinate (HPMCAS) and polyethylene glycol (PEG) formulations and subsequently feed them in the 3D printer. The shapes of the Starmix® objects were printed in the form of a heart, ring, bottle, ring, bear and lion. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infra-red Spectroscopy (FT-IR) and confocal Raman analysis were used to assess the drug – excipient interactions and the content uniformity.Results
Physicochemical analysis showed the presence of molecularly dispersed IND in the printed tablets. In vivo taste masking evaluation demonstrated excellent masking of the drug bitterness. The printed forms were evaluated for drug dissolution and showed immediate IND release independently of the printed shape, within 60 min.Conclusions
3D printing was used successfully to process drug loaded filaments for the development of paediatric printed tablets in the form of Starmix® designs.7.
Cappellini MD Bejaoui M Agaoglu L Porter J Coates T Jeng M Lai ME Mangiagli A Strauss G Girot R Watman N Ferster A Loggetto S Abish S Cario H Zoumbos N Vichinsky E Opitz H Ressayre-Djaffer C Abetz L Rofail D Baladi JF 《Clinical therapeutics》2007,29(5):909-917
BACKGROUND: Iron chelation therapy (ICT) with deferoxamine (DFO), the current standard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia, requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence, resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox is an orally administered iron chelator that has been approved for use in the United States, Switzerland, and other countries. OBJECTIVE: This analysis was conducted to compare patient-reported outcomes (PROs) during receipt of DFO infusions or once-daily oral therapy with deferasirox (ICL670). METHODS: PROs were prospectively evaluated as part of a randomized, Phase III study comparing the efficacy and safety profile of DFO 20 to 60 mg/kg per day with those of deferasirox 5 to 30 mg/kg per day in patients (age > or =2 years) with beta-thalassemia who were receiving regular transfusions and had a liver iron concentration of > or =2 mg/g dry weight. PRO questionnaires were completed by patients or a parent or legal guardian at baseline, week 4, week 24, and end of study (EOS). Patients assessed their level of satisfaction with study treatment (very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied) and rated its convenience (very convenient, convenient, neutral, inconvenient, or very inconvenient). Time lost from normal activities due to ICT in the previous 4 weeks was recorded using a single global assessment. At week 4, patients who had previous experience with DFO were asked to indicate their preference for treatment (ICT received before the study, ICT received during the study, no preference, or no response) and the reason for that preference. At EOS, all patients were asked if they would be willing to continue using the ICT they had received during the study. All study analyses were performed in all patients who received at least 1 dose of study medication. RESULTS: Five hundred eighty-six patients (304 females, 282 males; age range, 2-53 years) received treatment with DFO (n = 290) or deferasirox (n = 296). Significantly more patients treated with deferasirox reported being very satisfied or satisfied with treatment compared with those treated with DFO (week 4: 92.0% vs 50.4%, respectively; week 24: 89.6% vs 44.0%; EOS: 85.1% vs 38.7%; all, P < 0.001). At the same time points, the majority of those treated with deferasirox reported that treatment was very convenient or convenient compared with those treated with DFO (95.5% vs 21.3%, 91.7% vs 17.4%, and 92.7% vs 11.3%, respectively; all, P < 0.001). Among patients who had previously taken DFO and were randomized to receive deferasirox during the study, 96.9% reported a preference for deferasirox over DFO. At EOS, the proportion of patients indicating a willingness to continue study therapy was significantly greater in those receiving deferasirox than in those receiving DFO (85.8% vs 13.8%; P < 0.001). CONCLUSIONS: In this study, patient-reported satisfaction and convenience were significantly higher for the once-daily, oral ICT deferasirox than for DFO infusions. Among patients who had received DFO before the study, the majority indicated a preference for deferasirox over DFO. Most patients receiving deferasirox indicated that they would be willing to continue taking it. These results suggest that deferasirox had a positive impact on patients' daily lives. 相似文献
8.
Panagiotis Lepetsos Andreas Pampanos Emmanouil Kanavakis Maria Tzetis Dimitrios Korres Athanasios G. Papavassiliou Nicolaos Efstathopoulos 《Journal of orthopaedic research》2014,32(9):1155-1160
9.
Chronic kidney disease constitutes a highly prevalent health problem worldwide. Left untreated, it progresses inexorably to greater levels of severity at variable rates. The morbid impact of chronic kidney disease is heightened by its role as risk factor for cardiovascular disease. In the past two decades, considerable gains have been realized in retarding progression of chronic kidney disease by emphasizing blood pressure control and blockade of the renin-angiotensin system. Notwithstanding, the therapeutic goal of preventing or arresting chronic kidney disease progression remains unfulfilled. Currently attainable rates of decrease in glomerular filtration rate remain at 2 to 8 mL/min/y depending on the underlying disease. It is now believed that to achieve optimal therapeutic targets (proteinuria of <500 mg/day and decrease in glomerular filtration rate of 1 mL/min/y, the average age-related decline) we must introduce novel strategies and a multifaceted approach to treatment that interrupts multiple mechanisms of progression. To this end, and wherever relevant, new approaches to cause-specific treatment must be applied, such as targeted immunosuppression, intensive glycemic control, gene therapy, and enzyme replacement therapy. Furthermore, in all chronic kidney disease, we must interfere more effectively with the multitude of common mechanisms of progression. Established or putative, such approaches include aggressive blood pressure control; advanced renin-angiotensin system blockade; cytokine modulation and antifibrotic therapy; aldosterone blockade; endothelin blockade, nitric oxide modulation and vasopeptidase inhibition; antioxidant therapy; statin therapy; glycosaminoglycan therapy; anemia therapy; dietary restrictions; lifestyle changes; and pharmacogenomic profiling. Such a concerted, multifaceted approach to management might indeed prevent or arrest progression of chronic kidney disease, or even achieve regression of chronic kidney disease. 相似文献
10.
Utility of Ki‐67, p53, Bcl‐2, and Cox‐2 biomarkers for low‐grade endometrial cancer and disordered proliferative/benign hyperplastic endometrium by imprint cytology 下载免费PDF全文
George Apostolou M.D. Nicolaos Apostolou PhD. Maria Biteli M.D. Nikolaos Kavantzas M.D. M.I.A.C. Efstratios Patsouris M.D. PhD. Paulina Athanassiadou M.D. PhD. 《Diagnostic cytopathology》2014,42(2):134-142
In this report, the authors examined the characteristic features of morphology and molecular biology of Ki‐67, p53, Bcl‐2, and cyclooxygenase‐2 (Cox‐2) immunocytochemistry in low‐grade endometrioid endometrial carcinoma (LG‐ENEC) and disordered proliferative (DP)/benign hyperplastic (BH) endometrium. We carried out a prospective study by collecting endometrial imprints from freshly resected uteri over a 20‐month period and finally 104 patients were evaluated with endometrial cytology. We focused on LG‐ENECs, as well as on BH endometrium and its precursor lesion, DP endometrium, firstly because of the overlapping cytomorphology of these pathologic entities and secondly because of the lack of agreement in the differential diagnosis of atypical hyperplasia from complex hyperplasia and well‐differentiated endometrial carcinoma, even in curettage specimens. Ki‐67 expression of LG‐ENEC showed predominance in comparison with DP/BH endometrium. Furthermore, high levels of Bcl‐2 (>50%) were expressed only in DP/BH endometrium. DP/BH endometrium was negative for p53 marker, except from two cases of BH endometrium. Cox‐2 expression ≥50% was found only in LG‐ENECs. Using Ki‐67, Bcl‐2, p53, and Cox‐2 markers, we managed to distinguish fully DP/BH endometrium from LG‐ENEC. Higher Ki‐67%/Bcl‐2% rate and also higher Cox‐2 expression were found in LG‐ENEC cases with FIGO stage ≥ IC, than in cases with FIGO stage < IC. The immunocytochemical findings from a combination of Ki‐67, p53, Bcl‐2, and Cox‐2, may differentiate LG‐ENEC from DP/BH endometrium with overlapping cytomorphology. Immunocytochemistry appeared to be useful also for the correlation between LG‐ENEC and FIGO stage. Diagn. Cytopathol. 2014;42: 134–142. © 2013 Wiley Periodicals, Inc. 相似文献