Maternal factors and associated anomalies in NTD fetuses from Tunisia

Aim of the study

To determine the impact of maternal age, consanguinity, season of conception and variation in the amount of amniotic fluid for the appearance of anomalies associated with neural tube defects (NTDs).

Materials and methods

150 NTD fetuses, a result from autopsies (macroscopic autopsy; microscopic study of biopsy fragments; macro and microscopic brain examination), have been examined during a period of three years (01.2006, 01.2009), in the Clinic of Fetopathology, at the Center of Maternity and Neonatology — Tunisia.

Results

Anomalies associated with NTDs occur three times more often in pregnancies with an abnormal amount of amniotic fluid. Also, their likelihood of cardiovascular and reproductive system anomalies is increased four times. Nearly 80% of the NTD fetuses conceived during the autumn-winter period have acrania. Women older than 35, are twice more likely to have underweight children and children with defects of the digestive system and hand. They are also three times more likely to have fetuses with endocrine system abnormalities. Anomalies incompatible with life occur twice as often in consanguineous unions.

Conclusion

The mother’s age, consanguinity, season of conception, and variation in the amount of amniotic fluid have considerable impact on the emergence of associated anomalies in fetuses with NTDs.     

Columnar metaplasia in a surgical mouse model of gastro‐esophageal reflux disease is not derived from bone marrow‐derived cell

The incidence of esophageal adenocarcinoma has increased in the last 25 years. Columnar metaplasia in Barrett's mucosa is assumed to be a precancerous lesion for esophageal adenocarcinoma. However, the induction process of Barrett's mucosa is still unknown. To analyze the induction of esophageal columnar metaplasia, we established a mouse gastro‐esophageal reflux disease (GERD) model with associated development of columnar metaplasia in the esophagus. C57BL/6 mice received side‐to‐side anastomosis of the esophagogastric junction with the jejunum, and mice were killed 10, 20, and 40 weeks after operation. To analyze the contribution of bone marrow‐derived cells to columnar metaplasia in this surgical GERD model, some mice were transplanted with GFP‐marked bone marrow after the operation. Seventy‐three percent of the mice (16/22) showed thickened mucosa in esophagus and 41% of mice (9/22) developed columnar metaplasia 40 weeks after the operation with a mortality rate of 4%. Bone marrow‐derived cells were not detected in columnar metaplastic epithelia. However, scattered epithelial cells in the thickened squamous epithelia in regions of esophagitis did show bone marrow derivation. The results demonstrate that reflux induced by esophago‐jejunostomy in mice leads to the development of columnar metaplasia in the esophagus. However, bone marrow‐derived cells do not contribute directly to columnar metaplasia in this mouse model.     

Evolution of the pfcrt T76 and pfmdr1 Y86 markers and chloroquine susceptibility 8 years after cessation of chloroquine use in Pikine, Senegal

The goal of the present study was to assess the evolution of the in vitro chloroquine resistance and also the prevalence of pfcrt T76 and pfmdr1 Y86 mutations in Pikine from 2000 while chloroquine (CQ) was the first-line treatment of malaria to 2009 when artemisinin-based combination therapies (ACTs) are in use. We genotyped pfcrt K76T and pfmdr1 N86Y polymorphisms by PCR-RFLP and assessed in vitro CQ susceptibility by double-site enzyme-linked pLDH immunodetection (DELI) assay in Plasmodium falciparum isolates collected in Pikine, Senegal. The proportions of the pfcrt T76 allele in the light of the three different treatment policies were 72.4?% before CQ withdrawal (2000 to 2003), 47.2?% while amodiaquine plus Fansidar was the first-line treatment (2004 to 2005), and 59.5?% since the ACT use was implemented (2006 to 2009). The prevalence of pfcrt T76 decreased significantly after CQ was stopped [X (2)?=?6.54, P?=?0.01 (2000-2003 versus 2004-2005)] and then slightly since ACTs have been implemented [X (2)?=?1.12, P?=?0.28 (2000-2003 versus 2006-2009)]. There were no significant differences on the prevalence of pfmdr1 Y86 throughout the three treatment policies. The DELI assay was carried out episodically in 2000 (n?=?36), 2001 (n?=?47), and 2009 (n?=?37). The mean IC(50)s of the isolates to CQ in 2000 versus 2009 and 2001 versus 2009 are significantly different (P?相似文献   

Predictive value of early radiological findings in inflicted traumatic brain injury

Aim: The aim of this study was to evaluate the value of early radiological investigations in predicting the long‐term neurodevelopmental outcome of patients with inflicted traumatic brain injury (ITBI). Methods: In 28 patients with ITBI, radiological investigations were performed during the acute phase of injury (0–3 days) and during the early post‐injury phase (4 days to 1 month). The clinical outcome in survivors (n = 24) was based on the Glasgow Outcome Score. Results: Four of 28 infants died and five were severely disabled. Six infants had moderate disability. Detection of changes in the basal ganglia (p < 0.000005) or brainstem (p < 0.01), diffuse oedema (p < 0.005), transtentorial herniation (p < 0.01), subarachnoid haemorrhage (p < 0.05) or parenchymal injury (p < 0.05) by neuroimaging during the first 3 days, and detection of changes in the basal ganglia (p < 0.0005) or brainstem (p < 0.05) or parenchymal injury (p < 0.01) during 1 month were significantly associated with poor long‐term outcome. Conclusion: Radiological findings during the first month were significantly associated with the long‐term outcome. Especially, basal ganglia lesions were associated with a poor outcome.     

Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance

Central tolerance can be mediated by peripheral dendritic cells (DCs) that transport innocuous antigens (Ags) to the thymus for presentation to developing T cells, but the responsible DC subsets remained poorly defined. Immature plasmacytoid DCs (pDCs) express CCR9, a chemokine receptor involved in migration of T cell precursors to the thymus. We show here that CCR9 mediated efficient thymic entry of endogenous or i.v. transfused pDCs. pDCs activated by Toll-like receptor (TLR) ligands downregulated CCR9 and lost their ability to home to the thymus. Moreover, endogenous pDCs took up subcutaneously injected fluorescent Ag and, in the absence of TLR signals, transported Ag to the thymus in a CCR9-dependent fashion. Injected, Ag-loaded pDCs effectively deleted Ag-specific thymocytes, and this thymic clonal deletion required CCR9-mediated homing and was prevented by infectious signals. Thus, peripheral pDCs can contribute to immune tolerance through CCR9-dependent transport of peripheral Ags and subsequent deletion of Ag-reactive thymocytes.     

Calcium signaling in mouse oocyte maturation: the roles of STIM1, ORAI1 and SOCE

Calcium handling is critical for the oocyte function, since the first steps of fertilization are dependent on the appropriate Ca(2+) mobilization to originate transient spikes of the cytosolic Ca(2+) concentration. It is well known that the Ca(2+) influx from the extracellular milieu is required to maintain this signaling in mammalian oocytes. However, the regulation of the Ca(2+) channels involved in this process is still unknown in oocytes. STIM1, a key regulator of store-operated Ca(2+) entry (SOCE), relocates in the mouse oocyte shortly after sperm stimulation, suggesting that SOCE is involved in the maintenance of cytosolic Ca(2+)-spiking in the fertilized oocyte. Here, we show that there is an up-regulation of the expression of STIM1 at the germinal vesicle breakdown stage, and this expression remains steady during following maturation stages. We found that oocytes express ORAI1, a store-operated Ca(2+) channel, and that ORAI1 expression level was stable during oocyte maturation. Immature oocytes showed no Ca(2+) entry and no increase in STIM1-ORAI1 colocalization in response to the store depletion induced by thapsigargin. On the contrary, in mature oocytes, STIM1-ORAI1 colocalization is enhanced 3-fold by depletion of Ca(2+) stores, enabling the activation of store-operated calcium channels and therefore Ca(2+) entry. Finally, the correlation between SOCE activation during the maturation of oocytes and STIM1-ORAI1 colocalization strongly suggests that ORAI1 is involved in the Ca(2+) entry pathway in the mature oocyte. SOCE up-regulation in the final stage of maturation is further evidence of a major role for SOCE in fully mature oocytes, and therefore in Ca(2+) signaling at fertilization.