Pre-pregnancy iron reserves, iron supplementation during pregnancy, and birth weight

Background

Early iron supplementation in women with sufficient reserves could provoke iron excess resulting in haemoconcentration and low infant birth weight (IBW).

Aim

To clarify the influence of early iron supplementation on maternal iron status and the IBW, taking into account pre-pregnancy iron deposits.

Study design

Longitudinal, prospective study.

Subjects

Healthy women volunteers (n = 82) intending to become pregnant.

Outcome measures

Women were grouped as a function of their pre-pregnancy (low or present) iron stores (serum ferritin (SF) < or ≥ 20 μg/L) and time of commencement of iron supplementation during pregnancy; “early” (< 20 weeks) or “late” (≥ 20 weeks). Obstetric and clinical history, smoking habit, dietary intake and iron biochemical parameters were obtained at pre-pregnancy as well as at 1st, 2nd and 3rd trimesters. Haemoglobin, MCV, SF and transferrin saturation (TS) were measured.

Results

Overall, 36% of the women had low iron stores at pre-pregnancy. The mean early supplementation with iron was 140.7 mg/d and the mean of late supplementation was 99.01 mg/d. Early supplementation improves the biochemical status of the mother and does not provoke a significant increase in haemoconcentration relative to late supplementation independently of the pre-pregnancy iron levels.Supplemental iron had a positive effect on birth weight among women with pre-pregnancy low iron stores (β = 4.37; SE = 1.8; p = 0.038) and did not affect birth weight among women with present iron stores (β = − 0.008; SE = 3.03; p = 0.998).

Conclusion

Early iron supplementation with doses ~ 100 mg/d improves the biochemical status of the mother independently of her pre-pregnancy iron status. Supplementation with iron improves newborn birth weight in those women who start pregnancy with iron deficiency, and makes no significant difference to those women who are not iron deficient.     

tPA receptors and the fibrinolytic response in multiple sclerosis lesions

Axonal damage in multiple sclerosis (MS) lesions is associated with failure of fibrinolysis because of the inhibition of the plasminogen activator system. Plasma membrane receptors for tissue plasminogen activator (tPA) and plasminogen concentrate proteolytic activity on the cell surface and provide protection from inhibitors that in turn may locally enhance the fibrinolytic response. Therefore, we have investigated expression of two of these receptors in MS lesions, annexin II tetramer (AIIt) and low-density lipoprotein receptor-related protein (LRP). In acute MS lesions both AIIt and LRP were immunolocalized on macrophages and astrocytes while LRP was additionally found on neuronal cells in cortical gray matter. Western blot analysis confirmed a significant increase in AIIt in MS lesions and in a proportion of normal-appearing white matter samples, with a highly significant correlation between annexin II levels and factors associated with impeded fibrinolysis, such as plasminogen activator inhibitor-1. Immunoblotting analysis of plasmin(ogen) revealed increased levels of lysine-plasminogen in samples expressing high AIIt protein levels. Our results suggest that limited availability of tPA in MS lesions because of formation of tPA-plasminogen activator inhibitor-1 complexes reduces capability of tPA receptors to generate plasmin, which further diminishes fibrinolytic capacity in active MS lesions and possibly leads to axonal damage.     

In Vitro and In Situ Characterization of Fish Thymic Nurse Cells

We present an enzyme- and immuno-cytochemical, and ultrastructural characterization of trout thymic nurse cells (TNCs). Our data suggest that isolated trout thymic multicellular complexes are epithelial cells with acidic compartments that may be involved in the processing of antigens and in the generation of the MHC-II proteins that these cell express, and also that isolated TNCs are the In Vitro equivalent of the pale and intermediate electronlucent epithelial cells located in the inner zone of the trout thymus, constituting indirect evidence of the phylogenetical relationships of the inner zone of the teleost thymus with the thymic cortex of higher vertebrates.     

Characterization of the human jumonji gene

While constructing a cDNA library of human embryos, we have isolated a clone homologous to jumonji, a mouse gene required for neural tube formation. We have determined the complete coding sequence of the human homologue (JMJ) and deduced the amino acid sequence of the putative protein. We show here that human and mouse jumonji putative proteins are homologous and present 90% identity. During human embryogenesis, JMJ mRNAs are predominantly expressed in neurons and particularly in dorsal root ganglion cells. They are also expressed in neurons of human adult cerebral cortex. In view of these observations, we propose JMJ as a candidate gene for developmental defects of the central nervous system in the human. The human JMJ gene maps at position 6p24-6p23.      

Local allergic rhinitis: concept, pathophysiology, and management

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy characterized by local production of specific IgE (sIgE) antibodies, a T(H)2 pattern of mucosal cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response with release of inflammatory mediators (tryptase and eosinophil cationic protein). Although the prevalence remains to be established, a number of patients previously given a diagnosis of nonallergic rhinitis or idiopathic rhinitis are now being classified as having LAR. Culprit allergens responsible include house dust mite, grass and olive pollens, and many others. For the diagnosis of LAR, neither skin prick testing nor determination of the presence of serum sIgE antibodies is useful, and a nasal allergen provocation test is needed to identify the culprit allergen or allergens. In a certain proportion of cases, local sIgE can be detected, and conjunctivitis, asthma, or both can be associated. Whether patients with LAR will have systemic atopy in the future is a matter of debate. Further studies are needed for examine the prevalence of this phenomenon in different areas, to improve the diagnostic methods to better identify these patients, and to develop therapeutic approaches, including the use of immunotherapy.     

A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13

The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.     

New empirical evidence of the validity of the Chronic Pain Acceptance Questionnaire: the differential influence of activity engagement and pain willingness on adjustment to chronic pain

Objective. The aims of this study were to examine the internal structure of the Spanish version of the Chronic Pain Acceptance Questionnaire and present new empirical evidence regarding its validity. Design and Methods. A sample of 315 chronic pain patients attending a pain clinic completed a battery of instruments to assess pain acceptance, general psychological acceptance, depression, anxiety, pain intensity, functional impairment, and current functioning. Results. Confirmatory factor analysis supported the validity of a 20‐item version with two subscales corresponding to two independent factors: Activity Engagement and Pain Willingness. Structural Equation Modelling showed that the association between pain intensity and anxiety and depression was fully mediated by Activity Engagement which partially mediated the association between pain intensity and functioning. Pain Willingness partially mediated the influence of pain intensity on functional impairment. Conclusions. These findings indicate the differential influence of both components on adjustment to chronic pain.     

Bone morphogenetic protein-2/4 signalling pathway components are expressed in the human thymus and inhibit early T-cell development

T-cell differentiation is driven by a complex network of signals mainly derived from the thymic epithelium. In this study we demonstrate in the human thymus that cortical epithelial cells produce bone morphogenetic protein 2 (BMP2) and BMP4 and that both thymocytes and thymic epithelium express all the molecular machinery required for a response to these proteins. BMP receptors, BMPRIA and BMPRII, are mainly expressed by cortical thymocytes while BMPRIB is expressed in the majority of the human thymocytes. Some thymic epithelial cells from cortical and medullary areas express BMP receptors, being also cell targets for in vivo BMP2/4 signalling. The treatment with BMP4 of chimeric human-mouse fetal thymic organ cultures seeded with CD34+ human thymic progenitors results in reduced cell recovery and inhibition of the differentiation of human thymocytes from CD4- CD8- to CD4+ CD8+ cell stages. These results support a role for BMP2/4 signalling in human T-cell differentiation.