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Diabetes mellitus is associated with disturbances in haemostasis that could contribute to the development of thrombotic complications.The present study was undertaken to determine the behavior of coagulation variables and fibrinolytic system in diabetes mellitus. Forty five diabetic patients and forty five matched controls were evaluated by doing the following haemostatic parameter, prothrombin time, partial thromboplastin time, thrombin time, coagulation factors assay II, VII, IX, & plasma fibrinogen, ADP-induced platelet aggregation, protein C, a2- antiplasmin, PAI and FDPs. Generally diabetic patients have high levels of fibrinogen, a2- antiplasmin, & PAI and lower level of protein C. Other haemostatic parameters did not show statistically significant difference between diabetic patients and control group. Significantally elevated levels of PAI, a2- antiplasmin together with low protein C level in diabetic patients may result in the disturbance of haemostatic balance favoring thrombotic events. Conclusion: High levels of plasma fibrinogen, a2A- antiplasmin with low plasma protein C activity could lead to a prothrombotic tendency in insulin dependent diabetic patients. Moreover, in non-insulin dependent diabetic patients, the above mentioned parameters together with high levels of ADP-induced platelet aggregation and plasminogen activator inhibitor may increase the risk of thrombotic complications. Obesity can be considered as an additional risk factor for development of thrombosis in diabetic patients. 相似文献
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Suraj Konnath George Deeksha Vishwamitra Roxsan Manshouri Ping Shi Hesham M. Amin 《Oncotarget》2014,5(14):5750-5763
NPM-ALK+ T-cell anaplastic large-cell lymphoma (ALCL) is an aggressive type of cancer. Standard treatment of NPM-ALK+ ALCL is CHOP polychemotherapy. Although patients initially respond favorably to CHOP, resistance, relapse, and death frequently occur. Recently, selective targeting of ALK has emerged as an alternative therapeutic strategy. ASP3026 is a second-generation ALK inhibitor that can overcome crizotinib resistance in non-small cell lung cancer, and is currently being evaluated in clinical trials of patients with ALK+ solid tumors. However, NPM-ALK+ ALCL patients are not included in these trials. We studied the effects of ASP3026 on NPM-ALK+ ALCL cell lines in vitro and on systemic lymphoma growth in vivo. ASP3026 decreased the viability, proliferation, and colony formation, as well as induced apoptotic cell death of NPM-ALK+ ALCL cells. In addition, ASP3026 significantly reduced the proliferation of 293T cells transfected with NPM-ALK mutants that are resistant to crizotinib and downregulated tyrosine phosphorylation of these mutants. Moreover, ASP3026 abrogated systemic NPM-ALK+ ALCL growth in mice. Importantly, the survival of ASP3026-treated mice was superior to that of control and CHOP-treated mice. Our data suggest that ASP3026 is an effective treatment for NPM-ALK+ ALCL, and support the enrollment of patients with this lymphoma in the ongoing clinical trials. 相似文献
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S. S. Meshaal R. E. El Hawary D. S. Abd Elaziz A. Eldash R. Alkady S. Lotfy A. A. Mauracher L. Opitz J. Pachlopnik Schmid M. van der Burg J. Chou N. M. Galal J. A. Boutros R. Geha A. M. Elmarsafy 《Clinical and experimental immunology》2019,195(2):202-212
Mutations affecting recombination activation genes RAG1 and RAG2 are associated with variable phenotypes, depending on the residual recombinase activity. The aim of this study is to describe a variety of clinical phenotypes in RAG-deficient patients from the highly consanguineous Egyptian population. Thirty-one patients with RAG mutations (from 28 families) were included from 2013 to 2017. On the basis of clinical, immunological and genetic data, patients were subdivided into three groups; classical T–B– severe combined immunodeficiency (SCID), Omenn syndrome (OS) and atypical SCID. Nineteen patients presented with typical T–B–SCID; among these, five patients carried a homozygous RAG2 mutation G35V and five others carried two homozygous RAG2 mutations (T215I and R229Q) that were detected together. Four novel mutations were reported in the T–B–SCID group; three in RAG1 (A565P, N591Pfs*14 and K621E) and one in RAG2 (F29S). Seven patients presented with OS and a novel RAG2 mutation (C419W) was documented in one patient. The atypical SCID group comprised five patients. Two had normal B cell counts; one had a previously undescribed RAG2 mutation (V327D). The other three patients presented with autoimmune cytopaenias and features of combined immunodeficiency and were diagnosed at a relatively late age and with a substantial diagnostic delay; one patient had a novel RAG1 mutation (C335R). PID disorders are frequent among Egyptian children because of the high consanguinity. RAG mutations stand behind several variable phenotypes, including classical SCID, OS, atypical SCID with autoimmunity and T–B+ CID. 相似文献
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Ezzeldeen S. El Denshary Mohammad A. Al-Gahazali Fathia A. Mannaa Hesham A. Salem Nabila S. Hassan Mosaad A. Abdel-Wahhab 《Experimental and toxicologic pathology》2012,64(7-8):753-760
Liver diseases are amongst the most serious health problems in the world today and hepatocellular carcinoma is one of the world's deadliest cancers. The aim of the current study was to evaluate the protective effect of sider honey and/or Korean ginseng extract (KGE) against carbon tetrachloride (CCl4)-induced hepato-nephrotoxicity in rat. Eighty male Sprague-Dawley (SD) rats were allocated into different groups and over a 4-week period, they orally received honey and/or KGE or were treated either with CCl4 alone (100 mg/kg b.w) or with CCl4 after a pretreatment period with honey, KGE or a combination of both. Clinical, clinico-pathological and histopathological evaluations were done and CCl4-treated groups were compared with rats receiving no treatment and with rats given honey, KGE or a combination of these substances. The results indicated that oral administration of CCl4 induced severe hepatic and kidney injury associated with oxidative stress. The combined treatment with CCl4 plus honey and/or KGE resulted in a significant improvement in all evaluated parameters. This improvement was prominent in the group receiving CCl4 after combined pretreatment with honey and KGE. Animals receiving honey and/or KGE (without CCl4-treatment) were comparable to the control untreated group. It could be concluded that honey and KGE protect SD rats against the severe CCl4-induced hepatic and renal toxic effects. Our results suggest that the protective activity of honey and KGE may have been related to their antioxidant properties. 相似文献
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Levetiracetam (LEV) is an approved drug for the treatment of some epileptic disorders. With few and controversial reports addressing its possible pharmacodynamic interactions, the current study aimed at studying the effect of LEV on isolated rat duodenal strips to enlighten its possible intestinal adverse effects using the isolated smooth muscle strips of rat duodenum. LEV showed a dose‐dependent inhibition in KCl (80 mm )‐induced contractions in normal Tyrode's solution. Moreover, preincubation with LEV (3 mm ) in K+‐rich/Ca2+‐free medium led to a significant decrease in the maximum contractions (Emax) coupled to a right shift of the cumulative CaCl2 concentration curves implying a possible Ca2+ channel blocking potential. In addition, LEV exhibited a typical noncompetitive inhibition in the cumulative carbachol concentration curves evidenced as a decrease in Emax without the alteration of EC50, thus eliminating any possible role of the muscarinic receptors in the relaxant effect. To rule out other possible relaxant mechanisms, tests were conveyed in Tyrode's solution containing either 100 μm l ‐NAME or 10 μm glimepiride to test the possible relaxant roles exhibited by nitric oxide (NO) and KATP channel opening, respectively. None of the tested pathways was involved in LEV‐mediated relaxation. Taken altogether, the results of the current study entail that LEV might exert a relaxant effect on intestinal smooth muscles through blocking L‐type voltage‐operated calcium channels, but not involving either NO release or KATP channel opening. 相似文献