Inhibition of nitric oxide synthase dramatically potentiates seizures induced by kainic acid and pilocarpine in rats

We investigated whether the severity of convulsions evoked by kainic acid and pilocarpine is modified in nitric oxide synthase inhibitor-treated rats. We found that chronic treatment (4 days) withN_w-nitro-l-arginine greatly potentiates seizures induced by both convulsants suggesting a potential role for nitric oxide in mechanisms regulating seizure induction and propagation.     

Late effects of a perinatal exposure to a 16 PAH mixture: Increase of anxiety-related behaviours and decrease of regional brain metabolism in adult male rats

Polycyclic Aromatic Hydrocarbons (PAHs) are ubiquitous pollutants originated from incomplete combustion processes. Ingestion of contaminated food is the main route of exposure for humans. These molecules are able to cross the placental barrier and are also found in breast milk. Since PAHs are neurotoxic agents, the potential adverse effects of a perinatal exposure of the developing brain is a key issue for public health especially concerning PAH mixture. In this study, female rats were exposed trough diet to a mixture of 16 PAHs, at doses of 2 μg/kg/day or 200 μg/kg/day during gestation and 1.5 μg/kg/day or 150 μg/kg/day during breast-feeding period. To assess late neurotoxic effects in male offsprings, behavioural and cognitive tests were carried out and histochemical analyses using cytochrome oxidase as a cerebral metabolism marker were performed on adult animals. Results showed that anxiety-related behaviours significantly increased in exposed animals, but there was no significant alteration of motor activity and learning and memory abilities. Several brain areas of the limbic system showed a neuronal hypometabolism in exposed animals. This work highlights that exposure to PAHs at early stages of brain development can cause later troubles on behaviour and that PAHs are able to partly alter the central nervous system metabolism on adulthood.     

Impact of Recurrent Floods on the Utilization of Maternal and Newborn Healthcare in Bangladesh

Maternal and Child Health Journal - Floods are one of the most common types of disasters in Bangladesh and lead to direct and indirect impacts on health. The aim of the study was to assess the...     

Childhood near‐tetraploid acute lymphoblastic leukemia: an EGIL study on 36 cases

Objectives: Patients with near‐tetraploid (karyotype: 81 – 103 chromosomes) acute lymphoblastic leukemia (NT‐ALL) constitute about 1% of childhood ALL and data reported on them are limited and controversial. The aim of the study was to enlarge the knowledge on these rarely occurring ALL. Methods: The members of the European Group for Immunophenotyping of Leukemias (EGIL) searched retrospectively their databases for NT‐ALL patients. Results: We collected data of 36 European children from seven European countries with NT‐ALL diagnosed since 1992. All patients reached complete remission (CR) after induction chemotherapy. Their blasts were negative for peroxidase and BCR‐ABL1. Ten children were diagnosed as T‐cell ALL (T‐ALL) EGIL categories (T‐I n = 2, T‐II n = 2, T‐III n = 3, T‐IV n = 3) and four displayed various structural chromosomal abnormalities. Eight of 10 T‐ALL remained in 1st CR; one died in CR from sepsis and one is alive in 2nd CR. Median survival was 88 (7–213) months. B‐cell precursor (BCP) ALL was diagnosed in 26 children. Thirteen were positive for ETV6‐RUNX1 and are alive in 1st CR for 32–147 months. Ten children were ETV6‐RUNX1 negative and remained in 1st CR for 16–163 months. One girl with hypodiploid and NT metaphases and ETV6‐RUNX1‐negative BCP‐ALL and one of two boys with NT‐BCP‐ALL not examined for ETV6‐RUNX1 died of infection after stem cell transplantation in 2nd/3rd CR. Secondary myelodysplastic syndrome developed in two patients with NT‐BCP‐ALL. Conclusions: Our data demonstrate immunophenotypic, cytogenetic, and molecular heterogeneity of NT‐ALL and favorable prognosis of most NT‐ALL across different immunophenotypic and/or genetic ALL subtypes.     

Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation

To study the role of the JAK2-V617F mutation in leukemic transformation, we examined 27 patients with myeloproliferative disorders (MPDs) who transformed to acute myeloid leukemia (AML). At MPD diagnosis, JAK2-V617F was detectable in 17 of 27 patients. Surprisingly, only 5 of 17 patients developed JAK2-V617F-positive AML, whereas 9 of 17 patients transformed to JAK2-V617F-negative AML. Microsatellite analysis in a female patient showed that mitotic recombination was not responsible for the transition from JAK2-V617F-positive MPD to JAK2-V617F-negative AML, and clonality determined by the MPP1 polymorphism demonstrated that the granulocytes and leukemic blasts inactivated the same parental X chromosome. In a second patient positive for JAK2-V617F at transformation, but with JAK2-V617F-negative leukemic blasts, we found del(11q) in all cells examined, suggesting a common clonal origin of MPD and AML. We conclude that JAK2-V617F-positive MPD frequently yields JAK2-V617F-negative AML, and transformation of a common JAK2-V617F-negative ancestor represents a possible mechanism.     

The immune imbalance in the second hit of pancreatitis is independent of IL-17A

Background

Severe acute pancreatitis (SAP) is characterised by two distinct clinical phases. Organ dysfunction and death is initially as a result of a systemic inflammatory response syndrome (SIRS). Systemic sepsis from infected pancreatic necrosis characterises the second phase, the so called 'second hit' of acute pancreatitis (AP). An immune imbalance during the second hit is postulated to contribute to the formation of the septic complications that occur in these patients. The pro-inflammatory T-helper (Th) 17 pathway has been shown to be an initiator of early SIRS in AP, however to date its role has not been established in the second hit in AP.