Importance of measuring pharmacologically active metabolites of edoxaban: development and validation of an ultra-high-performance liquid chromatography coupled with a tandem mass spectrometry method

Journal of Thrombosis and Thrombolysis - Although DOACs do not require regular measurements of their blood concentrations, clinical situations may require an assessment of their concentration....     

Deficient expression of leukocyte adhesion proteins. A new Tunisian case

Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency inherited as an autosomal recessive genetic disorder. LAD was suspected in a four days old girl. She was born from healthy first cousins. A family history of a boy who died from omphalitis and sepsis was reported. Our patient had the severe form, she had delayed umbilical cord separation and suffered recurrent infections. She had a deletion of the G at position 1497. The patient received bone marrow transplantation from her HLA-identical mother at age of 14 months. She is now 9 years old and in good health.     

ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells

Microtubules (MTs) contribute to key processes during cell motility, including the regulation of focal adhesion turnover and the establishment and maintenance of cell orientation. It was previously demonstrated that the ErbB2 receptor tyrosine kinase regulated MT outgrowth to the cell cortex via a complex including Memo, the GTPase RhoA, and the formin mDia1. But the mechanism that linked this signaling module to MTs remained undefined. We report that ErbB2-induced repression of glycogen synthase kinase-3 (GSK3) activity, mediated by Memo and mDia1, is required for MT capture and stabilization. Memo-dependent inhibition of GSK3 allows the relocalization of APC (adenomatous polyposis coli) and cytoplasmic linker-associated protein 2 (CLASP2), known MT-associated proteins, to the plasma membrane and ruffles. Peripheral microtubule extension also requires expression of the plus-end binding protein EB1 and its recently described interactor, the spectraplakin ACF7. In fact, in migrating cells, ACF7 localizes to the plasma membrane and ruffles, in a Memo-, GSK3-, and APC-dependent manner. Finally, we demonstrate that ACF7 targeting to the plasma membrane is both required and sufficient for MT capture downstream of ErbB2. This function of ACF7 does not require its recently described ATPase activity. By defining the signaling pathway by which ErbB2 allows MT capture and stabilization at the cell leading edge, we provide insights into the mechanism underlying cell motility and steering.     

Osteopetrosis with carbonic anhydrase II deficiency: report of 24 cases

Twenty four patients suffering from osteopetrosis caused by carbonic anhydrase II deficiency are colliged. This pathology seems to be frequent in Tunisia. Mental retardation is present in 52%, 85% of patients have short stature and 25% have optic atrophy. All affected subjects show craniofacial disproportion and dental anomalies. Twenty patients have at least one bone fracture. Metabolic acidosis is constant: it is profound during the first life decade. A severe selective reduction of carbonic anhydrase II in erythrocyte is confirmed in 18 cases. Osteosclerosis and defective skeletal modelling are constant, cerebral calcification can be seen at the scanner approximately at the age of two years and six months. All patients are homozygous for a splice junction mutation in intron 2 of the carbonic anhydrase II gene, this mutation does not seem to protect patients from bone fractures nor induce a severe metabolic acidosis.     

Effect of organic loading on rotating biological contactor efficiency

Organic loading (weight per unit time per volume) is useful for the design of rotating biological contactors (RBC) and for comparison with the other processes such as activated sludge or oxidation ponds. The present study puts emphasis on the significance of this control or design parameter because it allows direct comparison of the RBC system's performance when operated under various circumstances and with different kinds of wastewater. The results of the paper proved that, the COD removal in rotating biological contactor systems is a function of the organic loading rate. However, each of the wastewater concentration and flow rate are also influence on the system efficiency but theirs impact can be combined by the effect of organic loading. The majority of COD removal (40-85 % of the total removal depending on the organic loading applied) occurs in the first stages of the system. There is a strong correlation between the organic loading and the concentration of the suspended solids in the rotating biological contactor basin. At higher loadings higher concentrations noted. At a loading of about, (24 g/m(2).d) suspended solids were 225, 125, 35, and 25 mg/L in the first, second, third and, the fourth stage respectively. To achieve an effluent quality of (BOD 相似文献