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Effects of insulin and pathway inhibitors on the PI3K-Akt- mTOR phosphorylation profile in acute myeloid leukemia cells

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Signal Transduction and Targeted Therapy 2019年第1期4卷 504-515页

作者： Ina Nepstad kimberley joanne hatfield Ida Sofie Grønningsæter Elise Aasebø Maria Hernandez-Valladares Karen Marie Hagen Kristin Paulsen Rye Frode SBerven Frode Selheim Håkon Reikvam Øystein Bruserud Section for Hematology Department of Clinical ScienceUniversity of BergenBergenNorway Department of Immunology and Transfusion Medicine Haukeland University HospitalBergenNorway Department of Biomedicine Faculty of Medicine and DentistryUniversity of BergenJonas Lies vei 915009 BergenNorway Section for Hematology Department of MedicineHaukeland University HospitalBergenNorway

The phosphatidylinositol 3-kinase(PI3K)-Akt-mechanistic target of rapamycin(mTOR)pathway is constitutively activated in human acute myeloid leukemia(AML)cells and is regarded as a possible therapeutic *** is an agonist of this pathway and a growth factor for AML *** characterized the effect of insulin on the phosphorylation of 10 mediators in the main track of the PI3K-Akt-mTOR pathway in AML cells from 76 consecutive *** overall results showed that insulin significantly increased the phosphorylation of all investigated ***,insulin effects on the pathway activation profile varied among patients,and increased phosphorylation in all mediators was observed only in a minority of patients;in other patients,insulin had divergent *** gene expression profiling and proteomic/phosphoproteomic comparisons suggested that AML cells from these two patient subsets differed with regard to AML cell differentiation,transcriptional regulation,RNA metabolism,and cellular *** insulin-induced phosphorylation was associated with weakened antiproliferative effects of metabolic ***3K,Akt,and mTOR inhibitors also caused divergent effects on the overall pathway phosphorylation profile in the presence of insulin,although PI3K and Akt inhibition caused a general reduction in Akt pT308 and 4EBP1 pT36/pT45 *** Akt inhibition,the phosphorylation of upstream mediators was generally increased or *** contrast,mTOR inhibition reduced mTOR pS2448 and S6 pS244 phosphorylation but increased Akt pT308 *** conclusion,the effects of both insulin and PI3K-Akt-mTOR inhibitors differ between AML patient subsets,and differences in insulin responsiveness are associated with differential susceptibility to metabolic targeting.

关键词： metabolism myeloid mTOR

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Case Findings:Sodium Ferric Gluconate Complex and Fetal Bradycardia

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Maternal-Fetal Medicine 2023年第4期5卷 260-262页

作者： Madeline Droney Samuel Scovell joanne hatfield Erin Pender Department of Pharmacy University Health-Truman Medical Center Kansas City MO 64108USA

Anemia in pregnancy is a significant event that often requires treatment to prevent long term effects in the mother and the *** factors determine which iron preparation to use,including route and ease of administration,patient tolerability,safety,and *** case report summarizes two separate patient cases where sodium ferric gluconate complex was administered intravenously to pregnant women,resulting in fetal bradycardia and emergent cesarean procedures.

关键词： Pregnancy Fetal bradycardia Sodium ferric Ferrlecit Iron deficiency anemia Adverse drug reaction Adverse event.

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Management of urolithiasis in pregnancy

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Current Urology 2023年第1期17卷 1-6页

作者： kimberley Chan Taner Shakir Omar El-Taji Amit Patel John Bycroft Chou Phay Lim Nikhil Vasdev Urology Department Lister HospitalEast and North Hertfordshire NHS TrustStevenageSG14ABUK Radiology Department Lister HospitalEast and North Hertfordshire NHS TrustStevenageUK Gynaecology Department Lister HospitalEast and North Hertfordshire NHS TrustStevenageUK School of Life and Medical Sciences University of HertfordshireHatfieldUK

Urolithiasis is the most common cause of nonobstetric abdominal pain,resulting in 1.7 admissions per 1000 *** most commonly occurs in the second and third trimesters,with an incidence between 1∶125 and 1∶*** urinary system obstructions are challenging to manage in obstetric patients because they contribute to physiological and anatomical changes that result in patho-logical *** restricted use of computed tomography in diagnosing and managing urolithiasis is particularly *** ad-dition,a prompt diagnosis is required because the presence of renal calculi during pregnancy increases the risk of fulminating sepsis and preterm *** pregnancies are conservatively managed;however,1 in 4 requires surgical *** for surgi-cal interventions are complex and range from nephrostomy insertion to empirical stent placement or ***,a multi-disciplinary approach is required to optimize patient *** diagnosis and management of urolithiasis in pregnancy are *** reviewed the role,safety,advantages and disadvantages of diagnostic tests and treatment used to manage acute urinary obstructions in pregnancy.

关键词： Urolithiasis Renal colic Pregnancy Acutely obstructed kidney Hydronephrosis Gestation

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