Substrate Specificity of the Flavoenzyme BhaC1 That Converts a C-Terminal Trp to a Hydroxyquinone.

The preparation of protein-protein, protein-peptide, and protein-small molecule conjugates is important for a variety of applications, such as vaccine production, immunotherapies, preparation of antibody-drug conjugates, and targeted delivery of therapeutics. To achieve site-selective conjugation, selective chemical or enzymatic functionalization of proteins is required. We have recently reported biosynthetic pathways in which small, catalytic scaffold peptides are utilized for the generation of amino acid-derived natural products called pearlins. In these systems, peptide amino-acyl tRNA ligases (PEARLs) append amino acids to the C-terminus of a scaffold peptide, and tailoring enzymes encoded in the biosynthetic gene clusters modify the PEARL-appended amino acid to generate a variety of natural products. Herein, we investigate the substrate selectivity of one such tailoring enzyme, BhaC1, that participates in pyrroloiminoquinone biosynthesis. BhaC1 converts the indole of a C-terminal tryptophan into an o-hydroxy-p-quinone, a promising moiety for site-selective bioconjugation. Our studies demonstrate that BhaC1 requires a 20-amino acid peptide for substrate recognition. When this peptide was appended at the C-terminus of proteins, the C-terminal Trp was modified by BhaC1. The enzyme is sufficiently selective that only small changes to the sequence of the peptide are tolerated. An AlphaFold model for substrate recognition explains the selectivity of the enzyme, which may be used to install a reactive handle onto the C-terminus of proteins.

A biosynthetic pathway to aromatic amines that uses glycyl-tRNA as nitrogen donor.

Aromatic amines in nature are typically installed with Glu or Gln as the nitrogen donor. Here we report a pathway that features glycyl-tRNA instead. During the biosynthesis of pyrroloiminoquinone-type natural products such as ammosamides, peptide-aminoacyl tRNA ligases append amino acids to the C-terminus of a ribosomally synthesized peptide. First, [Formula: see text] adds Trp in a Trp-tRNA-dependent reaction and the flavoprotein AmmC1 then carries out three hydroxylations of the indole ring of Trp. After oxidation to the corresponding ortho-hydroxy para-quinone, [Formula: see text] attaches Gly to the indole ring in a Gly-tRNA dependent fashion. Subsequent decarboxylation and hydrolysis results in an amino-substituted indole. Similar transformations are catalysed by orthologous enzymes from Bacillus halodurans. This pathway features three previously unknown biochemical processes using a ribosomally synthesized peptide as scaffold for non-ribosomal peptide extension and chemical modification to generate an amino acid-derived natural product.

Change over time in adolescent smoking, cannabis use and their association: findings from the School Health Research Network in Wales.

BACKGROUND: While tobacco smoking has declined among UK youth in recent decades, cannabis use has begun to show some growth. Given their interrelationship, growth in cannabis use may act as a barrier to continued reduction in youth smoking. This paper assesses recent tobacco and cannabis use trends in Wales, and their association, to explore whether change in cannabis use might have impacted youth tobacco smoking prevalence. METHODS: Repeat cross-sectional data on tobacco and cannabis use were obtained from biennial Welsh Student Health and Wellbeing surveys between 2013 and 2019. Data were pooled and analysed using logistic regression with adjustment for school-level clustering. RESULTS: No change in regular youth tobacco smoking was observed between 2013 and 2019. In contrast, current cannabis use increased during this time, and cannabis users had significantly greater odds of regular tobacco smoking. After adjusting for change in cannabis use, a significant decline in youth tobacco smoking was observed (OR 0.95; 95% confidence intervals: 0.92, 0.97). CONCLUSION: Recent growth in cannabis use among young people in Wales may have offset prospective declines in regular tobacco smoking. Further reductions in youth smoking may require more integrated policy approaches to address the co-use of tobacco and cannabis among adolescents.

Small Molecule Channels Harness Membrane Potential to Concentrate Potassium in trk1Δtrk2Δ Yeast.

Many protein ion channels harness membrane potential to move ions in opposition to their chemical gradient. Deficiencies of such proteins cause several human diseases, including cystic fibrosis, Bartter Syndrome, and proximal renal tubular acidosis. Using yeast as a eukaryotic model system, we asked whether, in the context of a protein ion channel deficiency in vivo, small molecule channels could similarly harness membrane potential to concentrate ions. Trk potassium transporters use membrane potential to move potassium from a relatively low concentration outside cells (∼15 mM) to one of >10× higher inside (150-500 mM); trk1Δtrk2Δ are unable to concentrate potassium or grow in standard media. Here we show that potassium-permeable, but not potassium-selective, small-molecule ion channels formed by amphotericin B can harness membrane potential to concentrate potassium and thereby restore trk1Δtrk2Δ growth. This finding expands the list of potential human channelopathies that might be addressed by a molecular prosthetics approach.

Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia.

Loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) compromise epithelial HCO3- and Cl- secretion, reduce airway surface liquid pH, and impair respiratory host defences in people with cystic fibrosis1-3. Here we report that apical addition of amphotericin B, a small molecule that forms unselective ion channels, restored HCO3- secretion and increased airway surface liquid pH in cultured airway epithelia from people with cystic fibrosis. These effects required the basolateral Na+, K+-ATPase, indicating that apical amphotericin B channels functionally interfaced with this driver of anion secretion. Amphotericin B also restored airway surface liquid pH, viscosity, and antibacterial activity in primary cultures of airway epithelia from people with cystic fibrosis caused by different mutations, including ones that do not yield CFTR, and increased airway surface liquid pH in CFTR-null pigs in vivo. Thus, unselective small-molecule ion channels can restore host defences in cystic fibrosis airway epithelia via a mechanism that is independent of CFTR and is therefore independent of genotype.

Waterborne outbreak of gastroenteritis on the KwaZulu-Natal Coast, South Africa, December 2016/January 2017.

An unexpected increase in gastroenteritis cases was reported by healthcare workers on the KwaZulu-Natal Coast, South Africa, January 2017 with >600 cases seen over a 3-week period. A case-control study was conducted to identify the source and risk factors associated with the outbreak so as to recommend control and prevention measures. Record review identified cases and controls and structured-telephonic interviews were conducted to obtain exposure history. Stool specimens were collected from 20 cases along with environmental samples and both screened for enteric pathogens. A total of 126 cases and 62 controls were included in the analysis. The odds of developing gastroenteritis were 6.0 times greater among holiday makers than residents (95% confidence interval (CI) 2.0-17.7). Swimming in the lagoon increased the odds of developing gastroenteritis by 3.3 times (95% CI 1.06-10.38). Lagoon water samples tested positive for norovirus (NoV) GI.6, GII.3 and GII.6, astrovirus and rotavirus. Eleven (55%) stool specimens were positive for NoV with eight genotyped as GI.1 (n = 2), GI.5 (n = 3), GI.6 (n = 2), and GI.7 (n = 1). A reported sewage contamination event impacting the lagoon was the likely source with person-to-person spread perpetuating the outbreak. Restriction to swimming in the lagoon was apparently ineffective at preventing the outbreak, possibly due to inadequate enforcement, communication and signage strategies.

Links between deprivation and risk of violence-related injury: a qualitative study to identify potential causal mechanisms.

Background: Deprivation has been shown to have a greater effect on risk of violent injury among adolescent girls than boys, but the mechanisms underlying this association have not been identified. Methods: In this qualitative study designed to identify causal mechanisms, focus groups involving girls aged 14-16 years attending secondary schools in South Wales, UK, were convened. Schools were recruited based on a measure of area-level deprivation. Discussions were audio-recorded and transcripts analysed thematically. Results: Girls from more deprived areas tended not to participate in organized activities, obtained alcohol from multiple sources, consumed alcoholic drinks of varying strengths in both supervised and unsupervised settings, and tended not to feel trusted by their parents; this led to poor adolescent-parent communication. Girls from less deprived areas tended to participate in organized activities, obtain alcohol from parents, consume low strength alcohol in supervised settings, and have a trusting and communicative relationship with their parents. Conclusion: Deprivation may increase risk of adolescent girls sustaining violence-related injury by increasing their time spent in unsupervised environments, with alcohol and without parental knowledge.

Temporal association of rotavirus vaccination and genotype circulation in South Africa: Observations from 2002 to 2014.

BACKGROUND: Rotavirus vaccination has reduced diarrhoeal morbidity and mortality globally. The monovalent rotavirus vaccine was introduced into the public immunization program in South Africa (SA) in 2009 and led to approximately 50% reduction in rotavirus hospitalization in young children. The aim of this study was to investigate the rotavirus genotype distribution in SA before and after vaccine introduction. MATERIALS AND METHODS: In addition to pre-vaccine era surveillance conducted from 2002 to 2008 at Dr George Mukhari Hospital (DGM), rotavirus surveillance among children <5 years hospitalized for acute diarrhoea was established at seven sentinel sites in SA from April 2009 to December 2014. Stool specimens were screened by enzyme immunoassay and rotavirus positive specimens genotyped using standardised methods. RESULTS: At DGM, there was a significant decrease in G1 strains from pre-vaccine introduction (34%; 479/1418; 2002-2009) compared to post-vaccine introduction (22%; 37/170; 2010-2014; p for trend <.001). Similarly, there was a significant increase in non-G1P[8] strains at this site (p for trend <.001). In expanded sentinel surveillance, when adjusted for age and site, the odds of rotavirus detection in hospitalized children with diarrhoea declined significantly from 2009 (46%; 423/917) to 2014 (22%; 205/939; p<.001). The odds of G1 detection declined significantly from 2009 (53%; 224/421) to 2010-2011 (26%; 183/703; aOR=0.5; p<.001) and 2012-2014 (9%; 80/905; aOR=0.1; p<.001). Non-G1P[8] strains showed a significant increase from 2009 (33%; 139/421) to 2012-2014 (52%; 473/905; aOR=2.5; p<.001). CONCLUSIONS: Rotavirus vaccination of children was associated with temporal changes in circulating genotypes. Despite these temporal changes in circulating genotypes, the overall reduction in rotavirus disease in South Africa remains significant.

A systematic review of the effectiveness of interruptive medication prescribing alerts in hospital CPOE systems to change prescriber behavior and improve patient safety.

OBJECTIVES: To assess the evidence of the effectiveness of different categories of interruptive medication prescribing alerts to change prescriber behavior and/or improve patient outcomes in hospital computerized provider order entry (CPOE) systems. METHODS: PubMed, Embase, CINAHL and the Cochrane Library were searched for relevant articles published between January 2000 and February 2016. Studies were included if they compared the outcomes of automatic, interruptive medication prescribing alert/s to a control/comparison group to determine alert effectiveness. RESULTS: Twenty-three studies describing 32 alerts classified into 11 alert categories were identified. The most common alert categories studied were drug-condition interaction (n=6), drug-drug interaction alerts (n=6) and corollary order alerts (n=6). All 23 papers investigated the effect of the intervention alert on at least one outcome measure of prescriber behavior. Just over half of the studies (53%, n=17) reported a statistically significant beneficial effect from the intervention alert; 34% (n=11) reported no statistically significant effect, and 6% (n=2) reported a significant detrimental effect. Two studies also evaluated the effect of alerts on patient outcome measures; neither finding that patient outcomes significantly improved following alert implementation (6%, n=2). The greatest volume of evidence relates to three alert categories: drug-condition, drug-drug and corollary order alerts. Of these, drug-condition alerts had the greatest number of studies reporting positive effects (five out of six studies). Only two of six studies of drug-drug interaction and one of six of corollary alerts reported positive benefits. DISCUSSION AND CONCLUSION: The current evidence-base does not show a clear indication that particular categories of alerts are more effective than others. While the majority of alert categories were shown to improve outcomes in some studies, there were also many cases where outcomes did not improve. This lack of evidence hinders decisions about the amount and type of decision support that should be integrated into CPOE systems to increase safety while reducing the risk of alert fatigue. Virtually no studies have sought to investigate the impact on changes to prescriber behavior and outcomes overall when alerts from multiple categories are incorporated within the same system.

Norovirus epidemiology in South African children <5 years hospitalised for diarrhoeal illness between 2009 and 2013.

Public health interest in norovirus (NoV) has increased in recent years following improved diagnostics, global burden estimates and the development of NoV vaccine candidates. This study aimed to describe the detection rate, clinical characteristics and environmental features associated with NoV detection in hospitalized children <5 years with diarrhoea in South Africa (SA). Between 2009 and 2013, prospective diarrhoeal surveillance was conducted at four sites in SA. Stool specimens were collected and screened for NoVs and other enteric pathogens using molecular and serological assays. Epidemiological and clinical data were compared in patients with or without detection of NoV. The study detected NoV in 15% (452/3103) of hospitalized children <5 years with diarrhoea with the majority of disease in children <2 years (92%; 417/452). NoV-positive children were more likely to present with diarrhoea and vomiting (odds ratio (OR) 1·3; 95% confidence interval (CI) 1·1-1·7; P = 0·011) with none-to-mild dehydration (adjusted OR 0·5; 95% CI 0·3-0·7) compared with NoV-negative children. Amongst children testing NoV positive, HIV-infected children were more likely to have prolonged hospitalization and increased mortality compared with HIV-uninfected children. Continued surveillance will be important to consider the epidemic trends and estimate the burden and risk of NoV infection in SA.

Norovirus diversity in children with gastroenteritis in South Africa from 2009 to 2013: GII.4 variants and recombinant strains predominate.

From 2009 to 2013 the diversity of noroviruses (NoVs) in children (⩽5 years) hospitalized with gastroenteritis in South Africa was investigated. NoVs were genotyped based on nucleotide sequence analyses of partial RNA-dependent RNA polymerase (RdRp) and capsid genes. Seventeen RdRp genotypes (GI.P2, GI.P3, GI.P6, GI.P7, GI.P not assigned (NA), GI.Pb, GI.Pf, GII.P2, GII.P4, GII.P7, GII.P13, GII.P16, GII.P21, GII.Pc, GII.Pe, GII.Pg, GII.PNA) and 20 capsid genotypes (GI.1, GI.2, GI.3, GI.5, GI.6, GI.7, GI.NA, GII.1, GII.2, GII.3, GII.4, GII.6, GII.7, GII.10, GII.12, GII.13, GII.14, GII.16, GII.17, GII.21) were identified. The combined RdRp/capsid genotype was determined for 275 GII strains. Fifteen confirmed recombinant NoV strains circulated during the study period. NoV GII.P4/GII.4 (47%) and GII.Pe/GII.4 (18%) predominated, followed by GII.PNA/GII.3 (10%) and GII.P21/GII.3 (7%). Other prevalent strains included GII.Pg/GII.12 (6%) and GII.Pg/GII.1 (3%). Two novel recombinants, GII.Pg/GII.2 and GII.Pg/GII.10 were identified. In 2013 the replacement of GII.4 New Orleans 2009 and GII.P21/GII.3, which predominated during the early part of the study, with GII.4 Sydney 2012 and GII.PNA/GII.3 was observed. This study presents the most comprehensive recent data on NoV diversity in Africa.

Report of the 7th African Rotavirus Symposium, Cape Town, South Africa, 8th November 2012.

The 7th African Rotavirus Symposium was held in Cape Town, South Africa, on the 8th November 2012 as a Satellite Symposium at the First International African Vaccinology Conference. Over 150 delegates participated in this symposium including scientists, clinicians, health officials, policymakers and vaccine manufacturers from across Africa. Key topics discussed included rotavirus surveillance, rotavirus vaccine introduction, post rotavirus vaccine impact analysis and intussusception data and surveillance in Africa. The symposium provided early rotavirus vaccine adopter countries in Africa (South Africa, Ghana and Botswana) an opportunity to share up-to-date information on vaccine introduction, and allowed colleagues to share experiences in establishing routine rotavirus surveillance (Tanzania, Niger and Rwanda). Overall, the symposium highlighted the high burden of rotavirus in Africa, and the need to continue to strengthen efforts in preventing rotavirus diarrhoea in Africa.

Maternal tissue blood flow and oxygen saturation in pre-eclampsia and intrauterine growth restriction.

OBJECTIVE: To investigate the hypothesis that impaired maternal tissue perfusion occurs in pre-eclampsia and intrauterine growth restriction (IUGR) and this correlates with maternal tissue oxygenation. STUDY DESIGN: Strain gauge plethysmography was used to compare maternal calf blood flow during the third trimester in 16 women with pre-eclampsia, 6 women with IUGR and 16 normal pregnant controls. A Mediaid iPOX pulse oximeter was used to measure maternal tissue oxygenation in the three groups and these were compared with tissue blood flow. RESULTS: Maternal tissue blood flow was significantly reduced in pre-eclampsia compared to the two other groups (p=0.003). Blood flow was significantly reduced in pre-eclampsia compared to IUGR (p=0.03). However there was no difference in blood flow between normal pregnancy and IUGR groups (p=0.76). No significant difference was noted in maternal tissue oxygenation between the normal pregnancy, pre-eclampsia and IUGR groups (mean±S.E.M. [97.13±0.4, 96.69±0.33, 97.83±0.47 respectively], p=0.26). No correlation was noted between blood flow and tissue oxygenation in the three groups of women. CONCLUSION: We have demonstrated that reduced maternal resting tissue blood flow present in women with pre-eclampsia is not seen in women with IUGR and the reduction in blood flow in pre-eclampsia is not associated with changes in maternal tissue oxygenation.

Applicability of Bio-wipes for the collection of human faecal specimens for detection and characterisation of enteric viruses.

OBJECTIVE: To determine whether gastroenteritis viruses and other enteric viruses could be detected in faecal specimens collected with Bio-wipes. METHODS: Faecal specimens, self-collected with Bio-wipes, from 190 individuals (94 diarrhoeal, 93 non-diarrhoeal, 3 unknown) were screened for eight human enteric viruses (enterovirus, hepatitis A virus, adenovirus, astrovirus, norovirus GI and GII, sapovirus and rotavirus) by real-time (reverse transcription)-polymerase chain reaction. Rotaviruses and noroviruses from positive specimens were genotyped. RESULTS: At least one enteric virus could be detected in 82.6% (157/190) of faecal specimens. Mixed infections of up to four different viruses could be detected in both diarrhoeal and non-diarrhoeal specimens. Enteroviruses were detected most frequently (63.7%), followed by adenoviruses (48.4%) and noroviruses (32.2%). Genotyping was successful for 78.6% of rotaviruses and 44.8% of noroviruses. CONCLUSIONS: Bio-wipes provide a user friendly, easier method for stool collection that facilitates enteric virus detection and genetic characterisation.

Human G9P[8] rotavirus strains circulating in Cameroon, 1999-2000: Genetic relationships with other G9 strains and detection of a new G9 subtype.

Group A rotaviruses (RV-A) are the leading cause of viral gastroenteritis in children worldwide and genotype G9P[8] is one of the five most common genotypes detected in humans. In order to gain insight into the degree of genetic variability of G9P[8] strains circulating in Cameroon, stool samples were collected during the 1999-2000 rotavirus season in two different geographic regions in Cameroon (Southwest and Western Regions). By RT-PCR, 15 G9P[8] strains (15/89=16.8%) were identified whose genomic configurations was subsequently determined by complete or partial gene sequencing. In general, all Cameroonian G9 strains clustered into current globally-spread sublineages of the VP7 gene and displayed 86.6-100% nucleotide identity amongst themselves and 81.2-99.5% nucleotide identity with global G9 strains. The full genome classification of all Cameroonian strains was G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 but phylogenetic analysis of each gene revealed that the strains were spread across 4 or more distinct lineages. An unusual strain, RVA/Human-wt/CMR/6788/1999/G9P[8], which shared the genomic constellation of other Cameroonian G9P[8] strains, contained a novel G9 subtype which diverged significantly (18.8% nucleotide and 19% amino acid distance) from previously described G9 strains. Nucleotide and amino acid alignments revealed that the 3' end of this gene is highly divergent from other G9 VP7 genes suggesting that it arose through extensive accumulation of point mutations. The results of this study demonstrate that diverse G9 strains circulated in Cameroon during 1999-2000.

Placental angiogenin inhibitor (ribonuclease inhibitor), a novel gene in pre-eclampsia.

There is convincing evidence that imbalance between angiogenic and anti-angiogenic factors play an important role in the pathophysiology of pre-eclampsia. Angiogenin, a member of the RNase A super family, is a potent inducer of angiogenesis and serum levels are shown to be elevated in pre-eclampsia. We hypothesize that placental expression of angiogenin inhibitor which binds and blocks the activity of angiogenin is altered in pre-eclampsia and may play a role in its pathophysiology. Placental expression of angiogenin inhibitor was measured in term placentae of 15 women with preeclampsia and 16 normal pregnant controls. The women were matched for age, parity and gestational age. Placental tissue was collected immediately after delivery and stored at -80°C until studied. Angiogenin inhibitor gene expression was measured using real-time quantitative polymerase chain reaction (rt-QPCR). The results were standardized using the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as reference gene. The mRNA expression of angiogenin inhibitor gene was significantly increased in preeclamptic placentae compared to normal pregnant controls [0.44 (0.174-1.048) versus 0.091 (0.029-0.301), median and interquatile range, p=0.027 for pre-eclampsia and normal controls respectively]. There was no correlation between angiogenin inhibitor gene expression and maternal age, blood pressure, platelet count, gestation age, birth weight of the baby in pre-eclampsia and normal pregnancy. This study showed that placental expression of the angiogenin inhibitor gene is significantly increased in pre-eclampsia and may play a role in its pathophysiology.

A novel hysteroscopic technique for the accurate biopsy of decidua parietalis and basalis.

BACKGROUND: Discrepancies in the results from studies of early events in human trophoblast invasion of decidua have been acknowledged and are attributed largely to deficiencies in the accuracy of sampling of the decidual tissue used in the research. We describe a novel technique of biopsy of decidua parietalis and basalis that overcomes the issue of accuracy of site of the biopsy. METHODS & RESULTS: The technique is applicable to pregnancies undergoing first trimester surgical termination. Following cervical dilatation, a rigid hysteroscope is introduced into the cervical canal. The pressure of the saline distending medium shears the membranes of the gestation sac away from the decidua parietalis, leaving the pregnancy suspended at the site of the early placenta (the decidual basalis). Under direct vision a biopsy forceps is used to sample the decidua parietalis, and then the forceps is introduced beneath the gestation sac to sample the decidua basalis. Morphological and immunohistochemical studies have confirmed the accuracyof site and adequacy of the samples, with a 40% myometrial spiral artery success rate. CONCLUSION: This is a simple novel technique of decidual biopsy under direct vision which allows for high accuracy of the site of biopsy material, and therefore has the potential to revolutionize research on trophoblast-decidua interactions during the critical early stages of human pregnancy.

Telescope alignment from sparsely sampled wavefront measurements over pupil subapertures.

We present a simple formalism that has proven useful in on-axis alignment of two-element telescopes when wavefront information is available from only a limited region (here two noncontiguous subapertures) of the pupil. Misalignments cause predictable full-aperture aberrations, which in turn cause predictable tip/tilt modes in the subapertures. For the most useful case in which secondary mirror tilts are independently constrained by optical monitoring, the four subaperture tip/tilt modes provide enough information to solve for the state of misalignment uniquely. A practically important and intuitively appealing simplification of this inversion occurs if the tip/tilts of the two subapertures are first transformed into a new basis consisting of differential and common-mode tilts in each of the x and y directions. Then the matrices interpreting subaperture modes as full-aperture aberrations and those in turn as mechanical misalignments become diagonal, so the mechanical adjustment required to align each degree of freedom is just a constant sensitivity multiplying one of the measured differential or common-mode tilt basis modes. Knowing that this simplification occurs allows rapid empirical calibration of sensitivities in the lab and then deterministic alignment, simply and transparently, with no need for ray tracing to model the optical effects of the adjustments at each step of the alignment.

PP011. Increased placental expression of angiogenin inhibitor (Ribonuclease inhibitor), a novel gene in pre-eclampsia.

INTRODUCTION: There is convincing evidence that imbalance between angiogenic and anti-angiogenic factors play an important role in the pathophysiology of pre-eclampsia. Increased expression of soluble fms-like tyrosine kinase-1 (sFlt1), along with decreased placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) appear to play a key role in the abnormal placentation and vascular dysfunction of pre-eclampsia. Angiogenin is a potent inducer of angiogenesis and serum levels are elevated in pre-eclampsia. Angiogenin Inhibitor (also called placental Ribonuclease inhibitor) is a potent antagonist of both angiogenic and ribonucloetic activities of angiogenin. We demonstrate that placental expression of angiogenin inhibitor is altered in pre-eclampsia and may play a role in its pathophysiology. OBJECTIVES: The aim of the study was to assess the expression of angiogenin inhibitor in healthy normotensive and pre-eclamptic placentas. METHODS: Placental expression of angiogenin inhibitor was measured in term placentae of 14 pre-eclamptic women and 16 normal pregnant controls. The women were matched for age, gestation and parity. Placental tissue was collected immediately after delivery and stored at -80°C. The angiogenin inhibitor gene expression was measured using real-time quantitative polymerase chain reaction (rt-QPCR). The results were standardized using the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) reference gene. RESULTS: mRNA expression of angiogenin inhibitor gene was significantly increased in pre-eclamptic placentae (p=0.027) compared to normal pregnant controls; 0.44 (0.174-1.048) versus 0.091 (0.029-0.301), median and interquartile range, for pre-eclampsia and normal controls, respectively. CONCLUSION: Placenta expression of angiogenin inhibitor gene is significantly increased in pre-eclampsia and may play a role in its pathophysiology. This finding may directly correlate with the reported ability of angiogenin inhibitor to protect from oxidative stress by its reactivity as an oxygen species scavenger.