Editorial: The placenta in pre-eclampsia-Lymphangiogenesis and angiogenesis

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The Use of Soluble FMS-like Tyrosine Kinase 1/Placental Growth Factor Ratio in the Clinical Management of Pre-eclampsia

Hypertensive disorders of pregnancy in particular the category preeclampsia (PE), remains a major cause of both maternal and fetal morbidity and mortality. Angiogenic growth factors (PlGF and VEGF) and their tyrosine kinase receptors -1 and 2 (Flt-1 and KDR) are involved in both fetal and placental development. Inadequate placentation and the consequent release of antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) is thus instrumental in the etiology of this disease. sFlt-1 binds to both angiogenic growth factors and neutralizes their effect thereby creating an angiogenic imbalance. This imbalance is frequently reported in women diagnosed with preeclampsia occurring before the clinical manifestation of the disease. The recent prognostic value of the sFlt-1/PlGF ratio has received considerable attention as a risk indicator of preeclampsia development. The aim of this review is to highlight the current advances in the diagnostic utility of the sFlt-1/PlGF ratio with regards to preeclampsia development. (Afr J Reprod Health 2018; 22[4]: 135-143).Keywords: Preeclampsia, sFlt-1, PlGF, treatment, predictio

Multiplex peptide microarray profiling of antibody reactivity against neglected tropical diseases derived B-cell epitopes for serodiagnosis in Zimbabwe

INTRODUCTION: Peptides (B-cell epitopes) have broad applications in disease diagnosis and surveillance of pathogen exposure. In this framework, we present a pilot study to design and produce a peptide microarray for the integrated surveillance of neglected tropical diseases. The peptide microarray was evaluated against peptides derived from Ascaris lumbricoides, Necator americanus, Schistosoma haematobium, Schistosoma mansoni, Trichuris trichiura, Bacillus anthracis, Mycobacterium leprae, Wuchereria bancrofti, Rabies lyssavirus, Chlamydia trachomatis and Trypanosoma brucei. METHODS: S. haematobium was diagnosed using the urine filtration technique. S. mansoni, A. lumbricoides, N. americanus and T. trichiura were diagnosed using the Kato Katz and formal ether concentration techniques. Immunogenic peptides were retrieved from the Tackling Infection to Benefit Africa infectious diseases epitope microarray. Further peptides were predicted using ABCpred. IgG and IgM reactivity against the derived peptides were evaluated using peptide microarray multiplex immunoassays. Positive response was defined as fluorescence intensity ≥ 500 fluorescence units. Immunodominant peptides were identified using color-coded heat maps and bar graphs reflecting the obtained fluorescence signal intensities. Receiver Operating Characteristic analysis and Mann-Whitney-U test were performed to determine the diagnostic validity of the peptides. RESULTS: Species-specific responses with at least one peptide derived from each NTD pathogen were observed. The reactive peptides included; for S. haematobium, XP_035588858.1-206-220 and XP_035588858.1-206-220 immunodominant for IgG and IgM respectively, for S. mansoni, P20287.1-58-72 immunodominant for both antibodies and for T. trichiura, CDW52482.1-326-340 immunodominant for IgG and CDW57769.1-2017-2031 and CDW57769.1-1518-1532 immunodominant for IgM. According to ROC analysis most of the peptides selected were inaccurate; with AUC < 0.5. Some peptides had AUC values ranging from 0.5 to 0.5875 for both IgM and IgG suggesting no discrimination. CONCLUSION: Multiplex peptide microarrays are a valuable tool for integrated NTDs surveillance and for screening parasites exposure in endemic areas. Species sero-reactivity observed in the study maybe indicative of exposure to the different NTDs parasites. However, although peptides with the least cross reactivity were selected there is need to validate the sero-reactivity with recombinant antigens and immune-blotting techniques such as western blotting

Dendritic and Synaptic Degeneration in Pyramidal Neurons of the Sensorimotor Cortex in Neonatal Mice With Kaolin-Induced Hydrocephalus

Obstructive hydrocephalus is a brain disorder in which the circulation of cerebrospinal fluid (CSF) is altered in a manner that causes expansion of fluid-filled intracranial compartments particularly the ventricles. The pyramidal neurons of the sensorimotor cortex are excitatory in nature and their dendritic spines are targets of excitatory synapses. This study evaluated the effect of hydrocephalus on dendritic arborization and synaptic structure of the pyramidal neurons of the sensorimotor cortex of neonatal hydrocephalic mice. Sterile kaolin suspension (0.01 ml of 250 mg/mL) was injected intracisternally into day old mice. Control animals mice received sham injections. Pups were weighed and sacrificed on postnatal days (PND) 7, 14 and 21. Fixed brain tissue blocks were silver impregnated using a modified Golgi staining technique and immunolabeled with synaptophysin to determine dendritic morphology and synaptic integrity respectively. Data were analyzed using ANOVA at α0.05. Golgi staining revealed diminished arborization of the basal dendrites and loss of dendritic spines in the pyramidal neurons of hydrocephalic mice. Compared to age-matched controls, there was a significant reduction in the percentage immunoreactivity of anti-synaptophysin in hydrocephalic mice on PND 7 (14.26 ± 1.91% vs. 62.57 ± 9.40%), PND 14 (4.19 ± 1.57% vs. 93.01 ± 1.66%) and PND 21 (17.55 ± 2.76% vs. 99.11 ± 0.63%) respectively. These alterations suggest impaired neuronal connections that are essential for the development of cortical circuits and may be the structural basis of the neurobehavioral deficits observed in neonatal hydrocephalus

Morphological study of the effects of aqueous leaf extract of Xylopia aethiopica on the pancreas in diabetic rats

To investigate the histological and immunohistochemical effects of aqueous leaf extract of Xylopia aethiopica on the pancreas in streptozotocin-induced diabetic rats, 30 adult Wistar rats were divided into three groups (n=10). Group A was the control (administered with equivalent volume of citrate buffer), group B animals were made diabetic by a single intraperitoneal injection of streptozotocin dissolved in citrate buffer (65 mg/kg), group C animals were made diabetic as above and treated with 200mg/kg body weight of aqueous leave extract of Xylopia aethiopica for 25 days. Upon animal sacrifice, the pancreas were excised, fixed in 10% formol saline and processed for light microscopy and immunohistochemistry.. The results revealed destruction of the islet cells in the untreated diabetic group as compared with the controls. The extract treated group was characterized by recovery/regenerative processes indicated by improvement in islet morphology. In untreated diabetic rats immunoreactive β-cells were sparse, at variance from the controls. The group treated with aqueous leaf extract of Xylopia aethiopica revealed more intense staining for insulin and significant (p&lt;0.05) increase in the percentage of immuno-labelled surface area when compared with the untreated diabetic group, suggesting the ability of β-cells to secrete insulin in the extract treated rats. We conclude that the aqueous leaf extract of Xylopia aethiopica improves recovery process of β-cells in streptozotocin-induced diabetic rats and might become useful in the management of diabetes related complications

Influence of Maternal Characteristics during Pregnancy on the Infant Early Life Immune Responses in a High HIV Burdened Setting in Harare, Zimbabwe

This study aimed at investigating the maternal characteristics that in turn influence the immunological status of infants in asymptomatic enteric pathogen carriers in mother baby pairs (MBPs) in a high HIV burdened population in Harare, Zimbabwe. BIOPLEX immunoassay was used to analyse serum samples from 39 MBPs for 27 cytokines and 6 immunoglobulins. The MBP were purposively selected based on HIV infection and Entamoeba histolytica carriage. Logistic regression was used to identify any link between maternal demographic and clinical data with infant cytokine and immunoglobulin levels. Maternal E. histolytica carriers were more likely to have infants with low levels of IL-12p70, FGF-basic, GM-CSF and TNF-α cytokines (OR: 0.14; 95% CI: 0.03-0.79) and high levels of IgA immunoglobulin (OR: 8.1; 95% CI: 1.45-45.06). HIV infected mothers were more likely to have infants with low levels of IgG2 (OR: 0.24; 95% CI: 0.06-1.00) and IgA (OR: 0.22; 95% CI: 0.05-0.90) immunoglobulins. Notably, it was highly likely to deliver infants with low IgG4 levels (OR: 0.24; 95% CI: 0.06-1.02) for maternal mean age above 30.38 years (Standard deviation 6.09) though not significant (p=0.05). Maternal E. histolytica asymptomatic carriage, and HIV-infection status result in low levels of pro-inflammatory cytokines IL-12p70, FGF-basic, GM-CSF and TNF-α and immunoglobulins IgG2, IgG4 and IgA on their infants.Keywords: Cytokines; Immunoglobulins; HIV infected mothers; enteric infections; Entamoeba histolytica; HIV-exposed infants

Analysis of dominant HIV quasispecies suggests independent viral evolution within spinal granulomas coinfected with mycobacterium tuberculosis and HIV-1 Subtype C

Extrapulmonary tuberculosis (TB) is a significant public health challenge in South Africa and worldwide, largely fuelled by the HIV epidemic. In spinal TB, Mycobacteria infect the spinal column without dissemination to the spinal cord. The immune microenvironment, target cell characteristics, and other evolutionary forces within granulomas during HIV/TB coinfection are poorly characterized. We investigated whether spinal TB granulomas represent a sequestered anatomical site where independent HIV evolution occurs, and assessed the role of macrophages as a target cell for both HIV and mycobacteria. RNA was extracted from plasma and granulomatous tissue from six antiretroviral-naive HIV-1/spinal TB-coinfected patients, RT-PCR amplified, and the C2-V5 env segment was cloned and sequenced. Analysis of genetic diversity, phylogeny and coalescence patterns was performed on clonal sequences. To investigate their role in HIV sequestration, macrophages and the HIV-1 p24 protein were immune localized and ultrastructural features were studied. Intercompartment diversity measurements and phylogenetic reconstruction revealed anatomically distinct monophyletic HIV-1 clusters in four of six patients. Genotypic CCR5-tropic variants were predominant (98.9%) with conservation of putative N-linked glycosylation sites in both compartments. CD68+ reactivity was associated with higher tissue viral load (r = 1.0; p 0.05). Ultrastructural imaging revealed the presence of bacterial and virus-like particles within membrane-bound intracellular compartments of macrophages. Spinal tuberculosis granulomas may form anatomically discreet sites of divergent viral evolution. Macrophages in these granulomas harbored both pathogens, suggesting that they may facilitate the process of viral sequestration within this compartment.This work was funded by a Wellcome Trust Grant. T. Ndung'u is funded through the South African DST/NRF Research Chair in Systems Biology of HIV/AIDS, the Victor Daitz Chair in HIV/TB Research, and an International Early Career Scientist Award from the Howard Hughes Medical Institute.http://online.liebertpub.com/aid2017-03-31hb2017Immunolog

THE ROLE OF HUMAN COMPLEMENT PROTEIN FACTOR B AND FACTORP/PROPERDIN IN HIV-ASSOCIATED PRE-ECLAMPSIA

Objectives This study seeks to discover how the concentration of complement proteins, factors B and P are affected in HIV-associated PE. Methods This study included 72 pregnant women: 36 preeclamptic and 36 normotensive. Serum concentrations of factors B and P were measured using a Bioplex immunoassay. Results A significant decrease of factor B in the HIV+ compared to the HIV- group was noted. No significant difference across all groups for both analytes was observed. Conclusion Our results suggest the alternative pathway (AP) is inhibited by HIV evading immune detection. The AP is not excessively activated in PE during the third trimester