Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment. 相似文献
Butyrylcholinesterase (BChE) is a serine esterase that plays a role in the detoxification of natural as well as synthetic ester-bond-containing compounds. Alterations in BChE activity are associated with a number of diseases. Cholinergic system abnormalities in particular are correlated with the formation of senile plaques in Alzheimer’s disease (AD), and administration of cholinesterase inhibitors is a common therapeutic approach used to treat AD.
Here, our aim was to study the interaction between BChE and fluoxetine.
Molecular docking simulations revealed that fluoxetine penetrated deep into the active-site gorge of BChE and that it was engaged in stabilizing noncovalent interactions with multiple subsites. In substrate kinetic studies, the Vm, Km, kcat and kcat/Km values were found to be 20.59?±?0.36?U mg?1 protein, 194?±?14?µM, 1.3?×?108?s?1 and 6.7?×?105?µM?1s?1, respectively. Based on inhibitory studies, fluoxetine appeared to inhibit BChE competitively, with an IC50 value of 104?µM and a Ki value of 36.3?±?4.7?µM.
Overall, both the low Ki value and the high number of BChE–fluoxetine interactions suggest that fluoxetine is a potent inhibitor of BChE, although in vivo mechanisms for the direct effects of BChE inhibition on various pathologies remain to be further investigated.
Acute generalized exanthematous pustulosis (AGEP) is seen uncommonly in children and sometimes shows atypical clinical features in this population. Patch testing can be used effectively in children for the confirmation of the culprit drug in cases of multiple drug use. Here, we report a rare, pediatric case of ceftriaxone‐induced AGEP confirmed by patch testing with subsequent recurrence of the skin eruption. 相似文献
Discontinuation of medication is the treatment of choice for patients with chronic daily headache (CDH) who overuse their medications. This treatment may be difficult due to increased headache severity observed in patients immediately after withdrawal. We retrospectively evaluated the efficacy of valproic acid therapy in 66 patients with overuse of CDH medication during withdrawal therapy. Patients were all withdrawn from medications and valproic acid started at 250 mg or 500 mg daily. Forty-two (63.6%) patients had decreased headache severity, including 27.3% objective responses in the first week. At the last visit in the 12th week, 50 patients were headache-free and only one patient had persistent headache. Fifteen patients withdrew from therapy due to side effects and lost to follow-up within this timeframe. Thus, low dose valproic acid appears to be safe and effective in the management of withdrawal therapy. 相似文献
Ischemia is the most important factor compromises wound healing in colonic anastomosis. Mesenteric vessels are ligated at
first while performing colonic resection and following anastomosis. Therefore blood supply of the related segments of colon
temporarily interrupted and ischemia can easily occur. This study was carried out to explore whether Bosentan, an endothelin-receptor
antagonist, can eliminate vasoconstruction, increase blood flow in the splanchnic area and anastomotic region and therefore
possibly facilitate wound healing and prevent intra-abdominal adhesion formation. 相似文献