Impaired renal endothelial nitric oxide synthase and reticulocyte production as modulators of hypertension induced by recombinant human erythropoietin in the rat

INTRODUCTION AND AIMS: Hypertension is a common side effect of recombinant human erythropoietin (rHuEPO) therapy; however, the exact pathways remain to be elucidated. The discovery of non-hematopoietic actions of rHuEPO increased the number of patients that could putatively benefit from this therapy; however, to achieve those effects higher doses are usually needed, which increase the risk and incidence of adverse events. Our aim was to study the effect of a broad range of rHuEPO doses on hematological and biochemical parameters, blood pressure and renal function and damage in the rat, focusing on endothelial nitric oxide synthase (eNOS) and hypoxia-inducible factors (HIFs). METHODS: Male Wistar rats were divided in 5 groups receiving different doses of rHuEPO (100, 200, 400 and 600 IU/kg body weight (BW)/week) and saline solution (control), during 3 weeks. Blood and 24h urine were collected to perform hematological and biochemical analysis. Blood pressure (BP) was measured by the tail-cuff method. The kidney tissue was collected to mRNA and protein expression assays and to characterize renal lesions. RESULTS: A dose-dependent increase in red blood cells count, hematocrit and hemoglobin levels was found with rHuEPO therapy, in rHuEPO200, rHuEPO400 and rHuEPO600 groups. Increased reticulocyte count was found in the rHuEPO400 and rHuEPO600 groups. BP raised in all groups receiving rHuEPO. The rHuEPO200 and rHuEPO600 groups presented increased kidney protein levels of HIF2α and a reduction in kidney protein levels of eNOS, along with the highest grade of vascular and tubular renal lesions. CONCLUSIONS: Our study showed that rHuEPO-induced hypertension might involve indirect (hematological) and direct (renal) effects which varies according to the dose used. Thus, rHuEPO therapy should be performed rationally and under adequate surveillance, as hypertension develops even with lower doses. Especial caution with higher doses should be taken, as rHuEPO-induced hypertension leads to early renal damage without alterations in traditional markers of renal function, thus masking the serious adverse effects and risks.

Peer interaction in mixed age groups: a study in the computer area of an early childhood education center in Portugal

The study was developed as a teacher-research project during initial teacher education – Masters Degree of Early Childhood and Primary Education, in Portugal. It analysed the interactions between children of 3 to 6 years old, during the use of the computer as a free choice activity, confronting situations between peers of the same age and situations between peers of different ages. The focus of the analysis was the collaborative interactions. This was a qualitative study. Children could choose the computer, amongst other interest areas, and work for around an hour in pairs. In the computer, children used mainly educational games. During four weeks, the interactions between the pairs were audio recorded. Field notes and informal interviews to the children were also used to collect data. Eleven children were involved in the study with ages ranging from 3 to 6 years old. Baseline data on children’s basic computer proficiency was collected using the Individualized Computer Proficiency Checklist (ICPC) by Hyun. The recorded interactions were analysed using the types of talk offered by Scrimshaw and Perkins and Wegerif and Scrimshaw: cumulative talk, exploratory talk, disputational talk, and tutorial talk. This framework was already used in a study in an early childhood education context in Portugal by Amante. The results reveal differences in computer use and characterize the observed interactions. Seven different pairs of children's interactions were analysed. More than a third of the interactions were cumulative talk, followed by exploratory talk, tutorial talk and disputational talk. Comparing same and mixed age pairs, we observed that cumulative talk is the more present interaction, but in same age pairs this is followed by exploratory talk whereas in the mixed age pairs it is tutorial talk that has the second largest percentage. The pairs formed by the children were very asymmetrical in terms of age and computer proficiency. This lead to the more tutorial interactions, where one children showed the other or directed him/her on how to play. The results show that collaboration is present during the use of a computer area in early childhood education. The free choice of the children means the adults can only suggest pairing suited to specific interactions between the children. Another way to support children in more exploratory talk interactions could be by discussing the way the older children can help the younger ones beyond directing or correcting their work.