Assessment of selected co-stimulatory, adhesion and activatory molecules and cytokines of Th(1)/Th(2) balance in acute lymphoblastic leukemia in children

INTRODUCTION: Recent years have seen a rise in the importance of cytokine production and co-stimulatory/activatory molecule expression in the immune response in leukemia. The aim of our study was to assess the function of T lymphocytes in children with acute lymphoblastic leukemia (ALL) during remission induction based on selected cytokine and co-stimulatory/activatory molecule expression. MATERIAL/METHODS: The study group consisted of 50 children with ALL (B cell precursor). Peripheral blood samples were taken before treatment (day 0), after the prednisone prophase (day 8), and during (day 15) and after (day 33) remission induction. The percentages of T cells with interferon (IFN)-gamma (Th(1)), interleukin (IL)-4 (Th(2)) and IL-2 receptor (IL-2R), CD28, CTLA-4, CD38, ICAM-1, and HLA-DR expression were assessed by tricolor flow cytometry. RESULTS: At the time of diagnosis we noted higher percentages of T cells with adhesion molecule ICAM-1, activation molecule CD38 expression, and an increased population of Th(2 )cells (IL-4) compared with the control group. During and after remission induction we observed a decreased population of CD38(+) T cells, elevated percentages of helper T lymphocytes with IL-2R expression, and a rise in helper T lymphocytes producing IFN-gamma (Th(1)). During fever/infection, higher levels of activated T lymphocytes (CD4(+)HLA-DR(+), CD8(+)HLA-DR(+)), a rise in Th1, and no change in Th(2 )populations were observed. CONCLUSIONS: The results suggest T cell activation and Th(2 )predominance at the time of diagnosis and during remission induction in ALL in children. These results confirm the involvement of cellular immunity in the leukemic process and can be used in immune therapy in leukemia.     

In vitro anti-hyperglycemia properties of the aqueous stem bark extract from Strychnos henningsii (Gilg)

Strychnos henningsii (SH) is a plant commonly used in southern African traditional medicine for the management of diabetes mellitus. Previous in vivo studies showed that a stem bark extract improves glycemic control in a diabetic animal model. Meanwhile, the mechanism of action has not been elucidated. The present study therefore investigated various in vitro models known to target glucose homeostasis and its direct complications. The plant extract was found to stimulate both basal and insulin stimulated glucose uptake in differentiated 3T3-L1 cells but not in Chang liver cells. The effect on 3T3-L1 cells appears independent of PPARγ as the extract did not stimulate adipogenesis. Although, SH extract was inhibitory toward intestinal alpha glucosidase, the physiological relevance is doubtful based on the recommended dosages. The extract strongly inhibited protein glycation which, at least in part, may be explained by the antioxidant and phenolic content of this plant. Cytotoxicity in Chang liver cells yielded an IC₅₀ value of 130.0 μg/mL raising concern that continual exposure to this herbal remedy may initiate hepatotoxicity. The finding from this study suggests that SH extract may attenuate hyperglycemia through enhanced peripheral tissue glucose utilization.     

Intellectual functioning of childhood leukemia survivors - relation to Tau protein - a marker of white matter injury

PurposeChemo- and radiotherapy used in acute lymphoblastic leukemia (ALL) can influence on brain functioning in the future. In a prospective study we analysed the cognitive functions of ALL survivors in relation to Tau protein as a marker of white matter injury.Material and methodsThirty-one survivors of childhood ALL (6.3 years after diagnosis); without the signs of CNS involvement, treated with chemotherapy alone, rested in first remission; underwent Intelligence tests- Wechsler Intelligence Scales (WISC-R, WAIS-R). Their results were analyzed in relation to the levels of Tau in cerebrospinal fluid (CSF) obtained during the treatment.ResultsThe analysis showed that all survivors attained the average scores in intelligence tests. A negative correlation was found between methotrexate (MTX) doses and Freedom from Distractibility (FFD). Females had higher values of Performance Intelligence Quotient (PIQ) than males. A negative correlation was noted of Tau protein levels obtained from the last CSF with: Total and Verbal Intelligence Quotient, PIQ, Perceptual Organisation Index and FFD but not with Verbal Comprehension Index.ConclusionOur results suggest the possibility of white matter injury during the treatment for ALL with chemotherapy alone. Elevated Tau protein level in CSF at the end of treatment might indicate future difficulties in neurocognitive functioning.     

Pharmacosimulation of delays and interruptions during administration of tirofiban: a systematic comparison between EU and US dosage regimens

Journal of Thrombosis and Thrombolysis - Tirofiban is a glycoproteine (GP) IIb/IIIa receptor antagonist, which inhibits platelet-platelet aggregation and is a potential adjunctive antithrombotic...     

Validation of forensic facial comparison by morphological analysis in photographic and CCTV samples

International Journal of Legal Medicine - Between the ever-increasing availability of surveillance evidence and expert-based forensic facial comparison being considered admissible in court,...     

Combination of in ovo electroporation and time‐lapse imaging to study migrational events in chicken embryos

Background : During embryonic development cell migration plays a principal role in several processes. In past decades, many studies were performed to investigate migrational events, occurring during embryonic organogenesis, neurogenesis, gliogenesis or myogenesis, just to name a few. Although different common techniques are already used for this purpose, one of their major limitations is the static character. However, cell migration is a sophisticated and highly dynamic process, wherefore new appropriate technologies are required to investigate this event in all its complexity. Results and Conclusions: Here we report a novel approach for dynamic analysis of cell migration within embryonic tissue. We combine the modern transfection method of in ovo electroporation with the use of tissue slice culture and state‐of‐the‐art imaging techniques, such as confocal laser scanning microscopy or spinning disc confocal microscopy, and thus, develop a method to study live the migration of myogenic precursors in chicken embryos. The conditions and parameters used in this study allow long‐term imaging for up to 24 hr. Our protocol can be easily adapted for investigations of a variety of other migrational events and provides a novel conception for dynamic analysis of migration during embryonic development. Developmental Dynamics 243:690–698, 2014. © 2013 Wiley Periodicals, Inc.     

Macrothrombosis and stroke in patients with mild Covid‐19 infection

Coronavirus disease 2019 (COVID‐19) is a pandemic disease currently affecting millions of people worldwide. Its neurological implications are poorly understood, and further study is urgently required. A hypercoagulable state has been reported in patients with severe COVID‐19, but nothing is known about coagulopathy in patients with milder disease. We describe cases of patients in New York City presenting with stroke secondary to large vessel thrombosis without occlusion, incidentally found to have COVID‐19 with only mild respiratory symptoms. This is in contrast to the venous thrombosis and microangiopathy that has been reported in patients with severe COVID‐19. Our cases suggest that even in the absence of severe disease, patients with COVID‐19 may be at increased risk of thrombus formation leading to stroke, perhaps resulting from viral involvement of the endothelium. Further systematic study is needed because this may have implications for primary and secondary stroke prevention in patients with COVID‐19.