Efficacy of Chemotherapy in Acute Leukemia Patients Resistant to Previous Standard Treatment According to the Series Measurement of WT1 Gene Expression

Aim. To estimate the efficacy of chemotherapy in acute leukemia patients resistant to previous standard treatment according to the series measurement of WT1 expression. Materials & Methods. The series measurement of WT1 expression formed the basis of the efficacy estimation of induction chemotherapy in 31 patients (15 men and 16 women aged from 3 months to 68 years; the median age was 28 years) with prognostically unfavourable variants of acute myeloid (AML) and lymphoblastic leukemia (ALL) (23 AML and 8 ALL patients). The WT1 gene expression was measured at baseline and 2–3 weeks after the treatment by the quantitative real-time PCR. The threshold level for detection was 250 copies of WT1/104 copies of ABL. The cytogenetic profile of leukemia cells was assessed by standard cytogenetics and FISH. Results. The baseline expression level of WT1 varied from 305 to 58,569 copies/104 copies of ABL. The expected reduction of WT1 expression after the first induction chemotherapy treatment was reported in 22/23 (96 %) AML patients and in 6/8 (75 %) ALL patients. According to our results WT1 expression reached the threshold in 13/31 (42 %) patients, including 9 AML patients and 4 ALL patients. After 11/31 (35 %) patients received the second course of treatment, WT1 expression level became normal in 8 cases (5 ALL and 3 AML patients). Despite high dose chemotherapy, HSCT and such agents as blinatumomab and gemtuzumab, an unfavourable outcome was observed in 18/31 (58 %) patients including 6 patients with complex karyotype (CK+) and 2 patients with monosomal karyotype (MK+). Once the MK+ and CK+ combination was observed, in another case the MK+ was combined with the prognostically unfavourable inv(3)(q21q26) inversion. Conclusion. Our results show that the molecular monitoring should be included as part of treatment of the prognostically unfavourable acute leukemia. The WT1 gene was shown to be the most appropriate marker. WT1 expression was shown to correlate with the common fusion genes allowing to estimate the blast cell count at the molecular level

Report of Didymocystis wedli Ariola, 1902 (Digenea; Didymozoidae) from Thunnus albacares in Brazil

Didymocystis wedli a parasite from the gills of Thunnus albacares from the coast of the State of Rio de Janeiro, is described by use of light and scanning electron microscopy. This is the first report of this species in Brazil and South America. New data are presented on the surface topography as demonstrated by scanning electron microscopy

Circadian rhythms and the kidney.

Numerous physiological functions exhibit substantial circadian oscillations. In the kidneys, renal plasma flow, the glomerular filtration rate and tubular reabsorption and/or secretion processes have been shown to peak during the active phase and decline during the inactive phase. These functional rhythms are driven, at least in part, by a self-sustaining cellular mechanism termed the circadian clock. The circadian clock controls different cellular functions, including transcription, translation and protein post-translational modifications (such as phosphorylation, acetylation and ubiquitylation) and degradation. Disruption of the circadian clock in animal models results in the loss of blood pressure control and substantial changes in the circadian pattern of water and electrolyte excretion in the urine. Kidney-specific suppression of the circadian clock in animals implicates both the intrinsic renal and the extrarenal circadian clocks in these pathologies. Alterations in the circadian rhythm of renal functions are associated with the development of hypertension, chronic kidney disease, renal fibrosis and kidney stones. Furthermore, renal circadian clocks might interfere with the pharmacokinetics and/or pharmacodynamics of various drugs and are therefore an important consideration in the treatment of some renal diseases or disorders