PROTEIN BOUND IODINE LEVEL IN CHILDREN WITH OBESITY

No abstrac

SERUM GLYCOPROTEINS IN RHEUMATIC CHILDREN

No abstract

СТРУКТУРА И ФАЗОВЫЙ СОСТАВ МНОГОСЛОЙНЫХ РЕНТГЕНОВСКИХ ЗЕРКАЛ W-Si

Методами рентгеновской дифрактометрии в жесткой области (l~0,154 нм) исследована фазовая структура, состав и строение многослойных рентгеновских зеркал (МРЗ) W/Si с толщиной слоев вольфрама tW2,7 нм слои вольфрама имеют поликристаллическую (ОЦК) структуру, а при tW<1,9 нм они аморфны. При помощи sin2Y-метода установлено, что в тонких кристаллических слоях вольфрама (tW<10 нм) может содержаться более 3 ат.% Si. Растягивающие напряжения в слоях кристаллического вольфрама не превышают 1,1 ГПа. Построение функций радиального распределения атомов позволило установить, что аморфные слои вольфрама имеют расположение атомов, близкое к b-W. Во всех образцах за счет взаимодействия на межфазных границах наблюдается формирование силицидных прослоек, в результате чего реальная толщина слоев вольфрама меньше номинальной. Аморфные силицидные прослойки, обязательно формирующиеся на стадии изготовления МРЗ, содержат дисилицид вольфрама. В зависимости от скорости осаждения дисилицид может иметь расположение атомов, близкое либо к тетрагональной фазе, t-WSi2 (~0,6 нм/с.), либо к гексагональной фазе, h-WSi2 (~0,15 нм/с.). Представлена уточненная модель строения аморфных МРЗ W/Si. Предложены механизмы формирования силицидных прослоек, согласно которым нижние силицидные прослойки (W-на-Si) формируются преимущественно за счет баллистического перемешивания атомов вольфрама и кремния, а верхние – вследствие диффузионного перемешивания. Сделана оценка коэффициентов взаимной диффузии, которые позволили установить, что осаждаемая поверхность слоев может быть разогрета, по меньшей мере, на 250° выше температуры подложки. Предложены пути снижения межфазного взаимодействия

Pivotal Role of Inosine Triphosphate Pyrophosphatase in Maintaining Genome Stability and the Prevention of Apoptosis in Human Cells

Pure nucleotide precursor pools are a prerequisite for high-fidelity DNA replication and the suppression of mutagenesis and carcinogenesis. ITPases are nucleoside triphosphate pyrophosphatases that clean the precursor pools of the non-canonical triphosphates of inosine and xanthine. The precise role of the human ITPase, encoded by the ITPA gene, is not clearly defined. ITPA is clinically important because a widespread polymorphism, 94C>A, leads to null ITPase activity in erythrocytes and is associated with an adverse reaction to thiopurine drugs. We studied the cellular function of ITPA in HeLa cells using the purine analog 6-N hydroxylaminopurine (HAP), whose triphosphate is also a substrate for ITPA. In this study, we demonstrate that ITPA knockdown sensitizes HeLa cells to HAP-induced DNA breaks and apoptosis. The HAP-induced DNA damage and cytotoxicity observed in ITPA knockdown cells are rescued by an overexpression of the yeast ITPase encoded by the HAM1 gene. We further show that ITPA knockdown results in elevated mutagenesis in response to HAP treatment. Our studies reveal the significance of ITPA in preventing base analog-induced apoptosis, DNA damage and mutagenesis in human cells. This implies that individuals with defective ITPase are predisposed to genome damage by impurities in nucleotide pools, which is drastically augmented by therapy with purine analogs. They are also at an elevated risk for degenerative diseases and cancer

Personalized therapy for mycophenolate: consensus report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.Personalised Therapeutic