The influence of synthetic tuftsin and its analogs on the function of granulocytes of children with acute lymphoblastic leukemia

The effect of tuftsin, its synthetic analogs and arginine on phagocytosis of Staphylococcus aureus by granulocytes from leukemic children was investigated in vitro. The high stimulatory effect of tuftsin and arginine was shown. The decrease of phagocytosis of PMN from healthy subjects after preincubation with its analogs and arginine was observed, suggesting the regulatory effect of these peptides.     

Lipid peroxidation in vitamin E-deficient rats submitted to subtotal nephrectomy

Clinical and experimental evidence has indicated that chronic renal failure (CRF) is related to increased free radical production. CRF patients show increased lipid peroxidation after a progressive reduction in vitamin E, one of the most important antioxidants. In the present study the role of vitamin E deficiency in lipid peroxidation was investigated in rats submitted to subtotal nephrectomy. Male Wistar rats were divided into groups receiving different diets for a period of 45 days: SND - sham rats submitted to a regular diet containing vitamin E; ERD nephrectomized rats submitted to a regular diet containing vitamin E; SDD - sham rats submitted to a vitamin E-deficient diet; EDD nephrectomized rats submitted to a vitamin E-deficient diet. After 30 days the Experimental animals were submitted to 5/6 nephrectomy and the Controls were submitted to sham operation. The vitamin E levels of the SDD and EDD groups were significantly reduced (p < 0.05) in plasma (4.92 +/- 1.22 and 8.37 +/- 2.09 mmol/L, respectively), liver (7.57 +/- 2.72 and 9.44 +/- 2.55mg/g tissue, respectively) and kidney (8.17 +/- 2.38 and 9.40 +/- 3.10 mg/g tissue, respectively) when compared to the SRD and ERD groups. In contrast, in the EDD group the levels of thiobarbituric acid-reactive substances, expressed as nmol/mg protein, were significantly increased (p < 0.05) in the liver (1.41 +/- 0.27) and kidney (1.67 +/- 0.47), and superoxide dismutase activity was significantly increased in the erythrocytes (4455.80 +/- 1322.63 Ug/Hb) compared to all other groups. The vitamin E-deficient diet associated with subtotal nephrectomy determined an increase in lipid peroxidation, suggesting an important role of free radicals in the development of chronic renal failure.     

Executive dysfunction in patients with chronic primary insomnia treated with clonazepam

Clonazepam (CNZ) is a drug used for insomnia treatment. Our objective was to search CNZ effects on executive functions (EF) in patients with chronic primary insomnia (CPI)-CNZ treated. Ninety participants were studied divided into three groups: a group of patients with CPI only (n = 30), a group of patients with CPI-CNZ treated (n = 30) and a healthy control drug-free subjects group (n = 30). EF were examined by means of E-Prime and by the Tower of London tests. Data of the EF were compared between groups, and correlation calculations between EF and CNZ dose were performed. Patients with CPI-CNZ treated showed more deleterious effects on EF (attention, inhibition, working memory, planning, cognitive flexibility, and monitoring) than patients with CPI only. Attention and cognitive flexibility correlated with CNZ dose. In conclusion, CNZ treatment was associated with deficits in some EF in patients with CPI-CNZ treated compared to CPI only and controls. We found a dose dependency between CNZ and some EF deficits.     

GATA3 germline variant is associated with CRLF2 expression and predicts outcome in pediatric B‐cell precursor acute lymphoblastic leukemia

The germline variant at rs3824662 in GATA3 is a risk locus for Philadelphia‐like acute lymphoblastic leukemia (Ph‐like ALL), the biological subtype of B‐cell precursor (BCP)‐ALL defined by a distinct gene expression profile and the presence of specific somatic aberrations including rearrangements of CRLF2. In this study, we investigated whether rs3824662 in GATA3 associates with CRLF2 expression in leukemic cells and predicts prognosis in pediatric BCP‐ALL patients treated according to the ALL Intercontinental Berlin‐Frankfurt‐Münster (IC BFM) 2009 (n = 645) and the ALL IC BFM 2002 (n = 216) protocols. High expression of CRLF2 was observed at both protein and mRNA levels (fourfold higher in AA than in CA + CC) among GATA3 AA variant carriers, independent of the presence of P2RY8‐CRLF2 fusion. Additionally, the AA variant at rs3824662 was a significant factor affecting minimal residual disease level at the end of induction phase and overall survival regardless of the risk group and the protocol. The germline variant at rs3824662 in GATA3 is a prognostic factor which associates with CRLF2 expression in leukemic cells supporting the hypothesis that GATA3 may have a regulatory effect on the CRLF2 pathway in pediatric BCP‐ALL.     

Frequent life-threatening laryngeal attacks in two Croatian families with hereditary angioedema due to C1 inhibitor deficiency harbouring a novel frameshift mutation in SERPING1

Objective: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease caused by mutations in the SERPING1 gene. It can affect many regions in the body, but potentially life-threatening laryngeal oedemas are of concern.

Methods: Twenty-three subjects from two families were recruited for clinical data evaluation and molecular analysis at General Hospital ?ibenik, Croatia.

Results: Decreased levels of C1 inhibitor were detected in 12 adult patients and three young asymptomatic persons. The same novel deletion of two nucleotides on exon 3 (c.74_75delAT) was identified in all of them. A history of laryngeal oedema was present in 10 patients (83%), and all patients reported laryngeal attacks at least once a year. The delay in diagnosis decreased noticeably from the first to the last generation.

Conclusions: We identified a novel causative mutation in SERPING1 in several affected members of two apparently unrelated families with a high frequency of laryngeal oedema. Molecular analysis of large C1-INH-HAE families will provide new insights on the genotype–phenotype relationship.

• Key messages

• Hereditary angioedema due to C1 inhibitor deficiency is a rare autosomal dominant disease caused by mutations in the SERPING1 gene, and laryngeal oedema is of concern because it can cause death by asphyxiation.

• A novel causative mutation in SERPING1, a deletion of two nucleotides on exon 3 (c.74_75delAT), was identified in several affected members of two apparently unrelated families with a high frequency of laryngeal oedema.

• Molecular analysis of large C1-INH-HAE families will provide new insights on the genotype–phenotype relationship because it appears that the mutation type may affect disease severity.

     

Sprawność fizyczna dzieci po leczeniu choroby nowotworowej

Background

Cancer, its treatment and long-term consequences of this treatment cause a significant reduction in physical activity in children. Lower level of physical activity is connected with limitation of physical fitness. The aim of this research project was to assess physical fitness in children after treatment for cancer.

Materials and Methods

The research covered 25 patients 6–14 years old after cancer treatment (13 boys and 12 girls). In 2008, 2009, 2010 and 2011 European Test of Physical Fitness (Eurofit) was used to evaluate children's physical fitness. Eurofit's results were classified in percentile reference curves made by Stupnicki et al. for Polish population of schoolchildren.

Results

Flexibility and static strength qualified in lower percentile ranges. Speed of limb movement results were better in subsequent years. The least significant change was observed in general balance.

Conclusions

Children after treatment for childhood cancer tend to have deficiencies in physical fitness. Their fitness level does not improve in time. There is even a tendency to achieve results qualified in lower percentile ranges in following years. Introducing a program of early physical development and promoting fitness activities, should counteract existing situation.