The impact of the duration of HAART on cytokine profiles in pregnancy.

OBJECTIVE: To determine the cytokine profile of HIV infected women treated with highly active anti-retroviral therapy (HAART) of variable duration in pregnancy. METHODS: HIV infected women were enrolled at a large tertiary hospital in Durban, South Africa in their antenatal period and stratified into those that initiated HAART before pregnancy (pre-pregnancy HAART or PPH group) and those who initiated HAART during pregnancy (in-pregnancy HAART or IPH group). These were compared with HIV negative women (HN group), matched for gestational age at the time of enrolment. Serum was obtained and Th1 and Th2 cytokines expression determined using the Bio-Plex Pro™ Human Cytokine Treg Panels. RESULTS: The overall cytokine profile of the cohort was pro-inflammatory as a result of significant IL-6 and TNF alpha expression. The anti-inflammatory markers (i.e. Th2 cytokines, namely IL4 and IL10) were poorly expressed by the whole cohort, with IL 4 seen almost exclusively in the IPH group, thus counter-balancing the predominantly pro-inflammatory milieu only in this group. PPH group had a pro-inflammatory milieu comparable to the HN control. IL 6 was the predominant cytokine in all groups, and as expected, it increased with advancing gestation in all the groups. This highly pro-inflammatory milieu was unexpected and needs further review CONCLUSION: Long use of HAART suppresses the anti-inflammatory markers previously reported to be conducive for the wellbeing of pregnancy. This effect needs further review as it was similarly observed in our HIV uninfected controls.

Maternal and perinatal outcomes after caesarean delivery in early and late onset preeclampsia with HIV positive and HIV negative South African Women.

OBJECTIVE: We analyzed the maternal and perinatal outcomes in early onset preeclampsia (EOPE) and late onset preeclampsia (LOPE) pregnant women who had scheduled caesarean deliveries. We sub-analyzed the two categories into HIV positive and HIV negative. PATIENTS AND METHODS: This prospective study was conducted at a regional hospital in Durban, South Africa during 14 months. A total of 14304 deliveries were registered. Out of the 1759 preeclampsia, 351 (19.9%) were EOPE and 1408 (80.1%) were LOPE. Hundred and twenty preeclamptics (n = 120) scheduled for caesarean delivery were selected and divided into two categories namely EOPE (n = 60) and LOPE (n = 60). Each preeclampsia category was then further stratified into HIV positive (n = 30) and HIV negative (n = 30) groups. Maternal demographic, clinical details for preeclampsia, blood laboratory tests, maternal, and perinatal outcomes were recorded. RESULTS: Women with EOPE were older compared to those with LOPE (P = 0.0001). Also the HIV positive women were older compared to the HIV negative groups in both EOPE and LOPE categories (P = 0.03). However, multiparous and primiparous were predominant in EOPE and LOPE categories, respectively (P = 0.00 and P = 0.00). The severity of hypertension and the HIV status did not differentiate the 2 groups. Overall, maternal complications (eclampsia, persistent postpartum hypertension, HELLP syndrome, maternal death) and poor fetal outcomes occurred predominately in EOPE. CONCLUSION: This study confirms the heterogeneity of preeclampsia and shows that the timing of onset of this pregnancy disorder is important to disease severity. Further HIV status influences maternal and neonatal outcome.

The role of trophoblast cell receptor expression in HIV-1 passage across the placenta in pre-eclampsia: an observational study.

OBJECTIVE: To compare expression of markers of HIV and associated receptors (p24, CD4, CCR5 and ICAM-2) in placentae and umbilical cords of HIV-associated and pre-eclamptic pregnancies to elucidate any association between these conditions in mother-to-child transmission. DESIGN: Cross-sectional immunohistochemical analysis of target receptor expression. SETTING: Laboratory-based study of primigravidae attending a district hospital in South Africa. POPULATION OR SAMPLE: Retrospectively collected placental tissue (stratified into four groups according to HIV status of normotensive and pre-eclamptic participants (n = 20/group). METHOD: Immunohistochemistry utilising CD4 (1:1), p24 (1:10), CCR5 (1:80) and ICAM-2 (1:100) antibodies was performed using light microscopy for image acquisition and analysis. MAIN OUTCOME MEASURES: Evaluate the expression of receptors on syncytiotrophoblast involved in in utero transmission of HIV. RESULTS: Syncytiotrophoblast was immunopositive for CD4 and CCR5 antibody with greater expression of CCR5 in HIV-positive versus HIV-negative groups (F1,159  = 6.979, P = 0.009) and normotensive versus pre-eclamptic groups (F1,159  = 8.803, P = 0.003). p24 was present in both placentae and umbilical cords of babies that were HIV-negative at 6 weeks. ICAM-2 immunostaining was observed in the syncytiotrophoblast across study groups and was significantly higher in the HIV-negative pre-eclamptic group (χ2 (3)  = 45.3; P < 0.001). CONCLUSION: Concurrent CD4 and CCR5 receptor expression demonstrates possible in utero viral entry routes across the placental barrier. ICAM-2 expression may influence HIV passage across the placenta or restoration of risk of pre-eclampsia in HAART-treated mothers. HIV was found in fetal circulation regardless of antiretroviral treatment. Further confirmatory ultrastructural and molecular work is warranted. TWEETABLE ABSTRACT: CD4, CCR5 and ICAM-2 on syncytiotrophoblast may facilitate HIV infection of passage across the placenta.

In vitro evaluation of metal chelators as potential metallo- ß -lactamase inhibitors.

AIMS: This study aimed at investigating the use of metal chelators as potential metallo-ß-lactamase inhibitors (MBL). METHODS AND RESULTS: The minimum inhibitory concentration (MIC) of meropenem was ascertained alone and in combination with various concentrations of macrocyclic (1,4,7- triazacyclononane-1-glutaric acid-4,7-diacetic acid = NODAGA) peptide derivatives and acyclic (N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine = TPEN and di-(2-picolyl)amine = DPA) metal chelators using the broth microdilution method. MICs of meropenem against carbapenem-resistant enterobacteriaceae (CRE) producing MBLs were decreased to concentrations as low as 0·06 mg l(-1) in the presence of some metal chelators. TPEN at 4 and 8 mg l(-1) showed the best activity by decreasing meropenem MICs to 0·5 and 0·06 mg l(-1) , respectively, for some New Delhi Metallo-beta-lactamase (NDM) and Verona integron-encoded metallo-ß-lactamase (VIM) -producing enterobacteriaceae. DPA at 8 and 16 mg l(-1) was also able to decrease meropenem MICs to 1 and 0·125 mg l(-1) , respectively, for these CREs. NODAGA peptide derivatives showed the least inhibition as 32 mg l(-1) was required for meropenem MICs to be decreased to 0·06 mg l(-1) against an NDM-1 producing isolate. CONCLUSION: The various metal chelators, TPEN, DPA and NODAGA peptide derivatives were able to inhibit the MBLs in decreasing order of activity, rendering CREs susceptible to meropenem. SIGNIFICANCE AND IMPACT OF THE STUDY: In the absence of new antibiotics, this study evaluated metal chelators as potential MBL inhibitors.

Myelin Sheath Injury in Kaolin-Induced Hydrocephalus: A Light and Electron Microscopy Study.

BACKGROUND: In hydrocephalus, the impairment of cognitive and motor functions is thought to be partly due to injury to the myelin sheath of axons in the central nervous system. The exact nature of this injury is not completely understood. METHODS: We induced hydrocephalus in 3-week-old rats with an intracisternal injection of kaolin suspension (0.04 ml of 200 mg/ml) and examined paraffin and ultrathin sections of the subcortical white matter from coronal slices of the cerebrum obtained at the level of the optic chiasm after sacrifice at weekly intervals for 4 weeks. RESULTS: Over time, there was a progression of injury to the myelin sheath consisting of attenuation, lamella separation and accumulation of myelin debris, focal degeneration, and the appearance of casts and loops. CONCLUSION: The results suggest that myelin injury in kaolin-induced hydrocephalus progresses with the duration and severity of ventriculomegaly.

Validation of a novel resin-porcine thorax model for chest drain insertion training.

Chest drain insertion in inexperienced hands carries a significant morbidity and mortality. The royal colleges, recognising this, stipulated that chest drain insertion be included as one of the core competences for all core medical trainees. However, there is no formal training in chest drain insertion included in training programmes. Simulation training should, in theory, provide a safe and objective method to overcome the obstacles in chest drain insertion training. There have been a number of attempts to find the ideal simulator for chest drain insertion with varying success. This article describes a model which is practical and affordable in all clinical skills labs, using porcine ribs mounted on a resin cast of a human thorax, and the data about the validation of the porcine-thorax model for chest drain insertion presented.

Effects of Ficus exasperata vahl. (moraceae) leaf aqueous extract on the renal function of streptozotocin-treated rats.

The present study was undertaken to evaluate the possible reno-protective effect of Ficus exasperata leaf aqueous extract (FEE) in a rat experimental paradigm of diabetes mellitus. Forty Wistar rats (weighing 200-230 g) were divided into four (A, B, C, and D) groups, each group consisting of 10 rats. Group A rats served as 'control' animals and received citrate buffer (pH 6.3) solution in quantities equivalent to intraperitoneally-administered volumes of streptozotocin (STZ) and FEE. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of STZ (75 mg/kg). Group C rats were additionally treated with FEE (100 mg/kg/day, p.o.) 4 weeks post STZ injections, for 4 consecutive weeks. Group D rats received FEE (100 mg/kg/day p.o.) only for 4 weeks. Post-euthanisation, kidney tissues were excised for histopathological evaluation and processed for light microscopy. Plasma malondialdehyde and tissue nitric oxide were determined. Serum creatinine, blood urea nitrogen, nitrite, and albumin concentrations were measured for the evaluation of renal function. The diabetic rats significantly lost more weight and their blood glucose levels were significantly elevated as compared to the 'control' group of animals. Renal dysfunction was evidenced by kidney hypertrophy, decreased renal blood flow, and increased serum creatinine and nitrite concentrations. Furthermore, vascular dysfunction, as evidenced by decreased carotid blood flow, was observed in the diabetic rats. FEE treatment positively ameliorated the alterations in the biochemical variables in the STZ + FEE-treated rats. In conclusion, our findings suggest that FEE treatment ameliorates STZ-induced nephrotoxicity.

Histopathological features in advanced abdominal pregnancies co-infected with SARS-CoV-2 and HIV-1 infections: A case evaluation.

Objectives: This study aims to provide a semi-qualitative histopathological report of the dual SARS-CoV-2 and HIV infected placentae in the third trimester of Advanced Abdominal Pregnancy (AAP). Study design: Four AAP placentae in the third trimester of pregnancy (two positive for HIV-1 and two positives for SARS-CoV-2) were histologically examined. Results: The SARS-CoV-2+ HIV+ placentae were dysmorphic in shape compared to the flattened disc-like shape noted in the SARS-CoV-2+HIV-, SARS-CoV-2-HIV+and SARS-CoV-2-HIV- placentae. Diffused syncytial knots and syncytial degeneration were observed in all placentae. Intermittent cytotrophoblast increase, perivillous and intravillous fibrin deposition, mononuclear inflammatory cells with widespread degeneration/necrosis of the syncytiotrophoblast and microcalcification were pronounced in the SARS-CoV-2+HIV+ compared to the SARS-CoV-2+HIV- placentae. Vascular pathological changes included thrombi, ectasis, mural hypertrophy and atherotic vessels. Conclusion: Elevated syncytial trophoblast injury, villitis, microcalcifications and mineralisation of the syncytial basement membrane in the AAP placentae may be due to SARS-CoV-2 viral transgression instead of HIV infection alone. Vascular malperfusion is suggestive of a hypoxic insult arising from a compensatory response to meet the fetal oxygen and nutrient demands of an AAP. Placentae from HIV infected women on antiretroviral treatment were characterised by vascular malperfusion.

Dental Caries Severity and Nutritional Status of Nigerian Preschool Children.

INTRODUCTION: Malnutrition in children is one of the most prevalent global health challenges, and malnourished children have a higher risk of death from childhood diseases. Early childhood caries (ECC) is the most common chronic disease of childhood. Complications from ECC such as pain, loss of tooth/teeth, and infection can undermine a child's nutrition and growth. AIM: This study aims to evaluate the severity of decay, missing, and filled tooth (dmft) by nutritional status using the z scores of the anthropometric measurements: height for age (HFA), weight for age (WFA), weight for height (WFH), and body mass index for age (BMIA) among children with ECC in Nigeria. STUDY DESIGN: This is a cross-sectional study conducted in 5 local government areas (LGAs) in Lagos State, Nigeria. A multistage sampling technique was used. RESULTS: A total of 273 cases of ECC were included in the analyses (mean age 4.19 ± 0.96 y). Overall, the mean dmft was 3.04 ± 2.28, and most (96%) were accounted for by untreated decay. The distribution of dmft within the different z score categories of BMIA (<-3 = severely wasted, -2 to -3 = wasted, -2 to +2 = normal, +2 to +3 = overweight and >+3 = obese) showed the highest dmft scores among the combined severely wasted and wasted groups, lowest among children with normal z scores, and intermediate in the overweight and obese groups. There was a significant negative correlation between BMIA z score, WFH z score, and dmft (r = -0.181, P < 0.05 and r = -0.143, P < 0.05, respectively). However, the correlations between HFA z score, WFA z score, and dmft were positive but not significant (r = 0.048, P = 0.44 and r = 0.022, P = 0.77, respectively). CONCLUSION: Our study showed an increased severity of dental caries among severely wasted or wasted children with ECC compared to those of normal or overweight. KNOWLEDGE TRANSFER STATEMENT: The results from this study will raise awareness among clinicians and policy makers on the need for a primary prevention program for early childhood caries in countries with high burden of malnutrition and limited resources. Also, it will help draw the attention of clinicians to the caries status of malnourished children that can be managed to improve the nutritional outcomes.

Genome-wide Gene-by-Sex Interaction Studies Identify Novel Nonsyndromic Orofacial Clefts Risk Locus.

Risk loci identified through genome-wide association studies have explained about 25% of the phenotypic variations in nonsyndromic orofacial clefts (nsOFCs) on the liability scale. Despite the notable sex differences in the incidences of the different cleft types, investigation of loci for sex-specific effects has been understudied. To explore the sex-specific effects in genetic etiology of nsOFCs, we conducted a genome-wide gene × sex (GxSex) interaction study in a sub-Saharan African orofacial cleft cohort. The sample included 1,019 nonsyndromic orofacial cleft cases (814 cleft lip with or without cleft palate and 205 cleft palate only) and 2,159 controls recruited from 3 sites (Ethiopia, Ghana, and Nigeria). An additive logistic model was used to examine the joint effects of the genotype and GxSex interaction. Furthermore, we examined loci with suggestive significance (P < 1E-5) in the additive model for the effect of the GxSex interaction only. We identified a novel risk locus on chromosome 8p22 with genome-wide significant joint and GxSex interaction effects (rs2720555, p2df = 1.16E-08, pGxSex = 1.49E-09, odds ratio [OR] = 0.44, 95% CI = 0.34 to 0.57). For males, the risk of cleft lip with or without cleft palate at this locus decreases with additional copies of the minor allele (p < 0.0001, OR = 0.60, 95% CI = 0.48 to 0.74), but the effect is reversed for females (p = 0.0004, OR = 1.36, 95% CI = 1.15 to 1.60). We replicated the female-specific effect of this locus in an independent cohort (p = 0.037, OR = 1.30, 95% CI = 1.02 to 1.65), but no significant effect was found for the males (p = 0.29, OR = 0.86, 95% CI = 0.65 to 1.14). This locus is in topologically associating domain with craniofacially expressed and enriched genes during embryonic development. Rare coding mutations of some of these genes were identified in nsOFC cohorts through whole exome sequencing analysis. Our study is additional proof that genome-wide GxSex interaction analysis provides an opportunity for novel findings of loci and genes that contribute to the risk of nsOFCs.

Neurotoxicity in pre-eclampsia involves oxidative injury, exacerbated cholinergic activity and impaired proteolytic and purinergic activities in cortex and cerebellum.

Women with a history of pre-eclampsia (PE) tend to have a higher risk of developing cardiovascular and neurological diseases later in life. Imbalance in oxidative markers and purinergic enzymes have been implicated in the pathogenesis of neurological disease. This study investigated the effect of PE on oxidative imbalance, purinergic enzyme inhibitory activity, acetylcholinesterase and chymotrypsin activities in the brain of PE rat model at post-partum/post-natal day (PP/PND) 60. Pregnant rats divided into early-onset and late-onset groups were administered with Nω-nitro-l-arginine methyl through drinking water at gestational days 8-17. Rats were allowed free access to water throughout the pregnancy and allowed to deliver on their own. The mother and the pups were euthanized at PP and PND 60, respectively, the cortex and the cerebellum excised, homogenized and stored for analyses of the enzymes. Results showed an increase in nitric oxide and malondialdehyde with a concomitant decrease in reduced glutathione and superoxide dismutase, an indication of oxidative damage. Also, there was an increase in acetylcholinesterase activity with a decrease in chymotrypsin, adenylpyrophosphatase and ecto-nucleoside triphosphate diphosphohydrolase activities in both the cortex and the cerebellum of the mother and the pups at PND 60. These results indicate the involvement of oxidative stress, increased cholinergic activity and depleted proteolytic and purinergic activities in PE-induced neurotoxicity.

Aminopeptidase A (ENPEP) gene polymorphisms and preeclampsia: Descriptive analysis.

OBJECTIVE: The etiology of preeclampsia (PE) remains elusive. Recent genome-wide association studies have identified a number of genetic variants associated with blood pressure variations in east Asians. One of the genetic variants is the aminopeptidase A (ENPEP) gene, which converts angiotensin II to angiotensin III. The C allele of rs6825911 is a risk for hypertension. The current study investigated whether genetic variants of ENPEP play a role in the pathogenesis of preeclampsia. STUDY DESIGN: The study was a descriptive analysis of gene polymorphisms of ENPEP; 602 pregnant women of African ancestry [normotensive (n = 245) and PE (n = 357)] were recruited. The two groups were divided according to their HIV status. The PE group consisted of early- and late-onset sub-categories. A single nucleotide polymorphism of rs6825911 was analyzed using the TaqMan® Probe mix and by means of real time polymerase chain reaction. RESULTS: The risk of C allele for PE was 1.07 (95 % CI 0.83-1.38, P = 0.589) for allele comparison and the risk for preeclampsia CC to CT/TT was 1.33 (95 % CI 0.96-1.85, P = 0.086). The sub analysis for the PE group without HIV infection the risk of C allele was 1.25 (95 % CI 0.838-1.78, P = 0.199) and the risk of PE of CC to CT/TT was 1.51 (95 %CI: 0.96-2.35, P = 0.071). CONCLUSION: This is the first study in a homogenous South African population of African ancestry to show that the variant of ENPEP gene does not play a role in pathogenesis of preeclampsia.

The Screening of Nails for Selected Essential and Toxic Elements in Normotensive and Pre-Eclamptic Women.

To compare the concentrations of 13 different elements in nail samples from pre-eclamptic and normotensive pregnant women. The study site was a regional hospital in Durban, KwaZulu Natal. Nail samples were collected from normotensive (n = 33) and pre-eclamptic (n = 33) pregnant women. Approximately 0.02 g of nail samples were digested in 70% nitric acid and analyzed using inductively coupled plasma-optical emission spectrometry. Analytes of interest were the following essential elements calcium (Ca), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), nickel (Ni), selenium (Se) and Zinc (Zn) as well as toxic elements, arsenic (As), cadmium (Cd) and lead (Pb). The observed concentrations of bioelements (mean, µg/g), Ca: normotensive (N) 3467 ± 197 vs (PE) 2897 ± 190; Mg: (N) 736 ± 61 vs (PE) 695 ± 59, were lower in pre-eclampsia albeit not statistically significant. Similarly, the observed concentrations of bioelements (mean, µg/g), Cd: (N) 3 ± 0.3 vs (PE) 2 ± 0.4; Co: (N) 3 ± 0.3 (PE) not detected; Mn: (N) 7 ± 1 (PE) 4 ± 0.8, were significantly lower in pre-eclampsia (p = 0.004, 0.0001 and 0.022, respectively). Therefore, this study demonstrated significantly lower levels of Cd, Co and Mn in pre-eclampsia which justifies the need for further research on these elements towards the effective management or prevention of pre-eclampsia which could ultimately also aid in establishing its pathogenesis.

Analysis of hepatocyte growth factor immunostaining in the placenta of HIV-infected normotensive versus preeclamptic pregnant women.

OBJECTIVE: Hepatocyte Growth Factor (HGF) plays a role in the migration and morphogenesis of different cell types and tissues. Preeclampsia (PE) is associated with deficient trophoblast invasion and placental insufficiency; hence HGF production is expected to be compromised. This study therefore aimed to immunolocalize and morphometrically analyse placental HGF in normotensive versus PE pregnancies stratified by HIV status and gestational age. STUDY DESIGN: Normotensive (N; n = 40) and preeclamptic (PE; n = 80) women were stratified by HIV status (HIV- and HIV+), and gestational age i.e. early onset of PE (EOPE; <34 weeks) and late onset of PE (LOPE; ≥34 weeks). Placental tissues were stained using conventional immunohistochemistry, performed using mouse anti-human HGF antibody. Morphometric image analysis was performed using Zeiss Axio-Vision software. RESULTS: HGF was immuno-localized within the syncytiotrophoblast, cytotrophoblast, endothelial and fibroblast-like cell populations of both conducting and exchange villi. Based on pregnancy type, HGF immunoexpression within the conducting villi was significantly different between Nvs EOPE (p = 0.0372) and EOPE vs LOPE (p = 0.0006). Within the exchange villi, no significant difference of HGF immunostaining was noted between N vs EOPE and N vs LOPE. A down-regulation of HGF immuno-expression was observed in LOPE compared to other groups within both villi types, albeit non-significant. Based on HIV status, no significant difference in HGF immuno-expression was demonstrated between HIV- vs HIV + within the exchange and conducting villi. However, the expression of HGF in HIV- group was elevated in both villi types. Across the groups, a significant difference was found between N+ vs EOPE- (p  = 0.0207), EOPE+ vs LOPE- (p = 0.0036) and EOPE- vs LOPE- (p = 0.0016) of the conducting villi while no significant difference was found within the exchange villi. CONCLUSION: This novel study demonstrates that HGF was two-fold higher in conducting compared to exchange villi irrespective of the pregnancy type. HIV infection does not influence HGF expression within the conducting and exchange villi. The HGF/c-MET receptor complex may modulate the ligand expression within the placenta.

Placental hypoxia inducible factor -1α & CHOP immuno-histochemical expression relative to maternal circulatory syncytiotrophoblast micro-vesicles in preeclamptic and normotensive pregnancies.

OBJECTIVES: Preeclampsia (PE) occurs as a result placental hypoxia-induced oxidative and endoplasmic reticulum stress, and is associated with the activation of hypoxia inducible factor-1α (HIF-1α) and apoptotic CHOP pathways with the consequential shedding of syncytiotrophoblast microvesicles which may be central in mediating the maternal systemic immune response. The aim of this study was to immune-localise and morphometrically analyse CHOP and HIF-1α within the placenta of normotensive and pre-eclamptic pregnancies and concomitantly quantify syncytiotrophoblast released microvesicles in maternal circulation. STUDY DESIGN: Placental tissue and plasma were obtained from normotensive and pre-eclamptic pregnant women. The expression of CHOP and HIF-1α was analysed using immunohistochemistry. Isolation and size distribution of the circulating maternal microvesicles was determined using nanoparticle tracking analysis. The concentration of syncytiotrophoblast microvesicles was determined using the placental alkaline phosphatase ELISA. RESULTS: This study demonstrates a significant increase in immunohistochemical expression of HIF-1 α and CHOP in preeclampsia compared to the normotensive women (p<0.05). In keeping with this, a significant increase in the mean syncytiotrophoblast microvesicles concentration was observed in PE, compared to normotensives (p<0.05). A positive correlation between placental expression of CHOP and HIF-1α and STBMs was obtained. CONCLUSION: This study demonstrates increased placental expression of HIF-1α and CHOP in preeclampsia compared to normotensive pregnancies which correlate to their increased syncytiotrophoblast microvesicles concentration in maternal circulation. These findings indicate that placental hypoxia and ER stress are interrelated contributory factors to the pathogenesis of PE and the consequential release of placental derived debris into the maternal circulation.

Elemental analysis of serum and hair from pre-eclamptic South African women.

Pre-eclampsia is a hypertensive disorder that is associated with adverse maternal and perinatal outcomes. It has been proposed that specific trace and macro elements associated with antioxidant activities may also play a contributory role in aetiology of pre-eclampsia. The aim of this study was to measure the concentrations of thirteen different elements in hair and serum samples from women with a diagnosis of pre-eclampsia and compare them with normotensive controls. Venous blood and pubic hair samples were collected from forty-three pre-eclamptic and twenty-three normotensive pregnant women. In each sample, the concentration of arsenic (As); calcium (Ca); cadmium (Cd); chromium (Cr); cobalt (Co); magnesium (Mg); manganese (Mn); iron (Fe); copper (Cu); lead (Pb); selenium (Se); nickel (Ni); zinc (Zn) were measured using inductively coupled plasma-optical emission spectrometry. Cobalt concentration in hair was significantly lower in the pre-eclampsia group (1.56±0.74µg/g) compared to the normotensive group (2.89±4.99µg/g) (p=0.02). The concentrations of Zn and Cr were significantly higher in hair samples from the pre-eclamptic group, compared to the normotensive control group (Zn, 395.99±48.60 vs 330.88±29.70µg/g; Cr, 13.31±2.67 vs 11.05±7.62µg/g: p≤0.05). There were no significant differences in the hair levels of other elements between groups. Serum Zn was significantly higher in the pre-eclamptic group (0.16-253.4mg/L) compared to the normotensive group (0.2-48.4mg/L) (p=0.01). Serum Ca, Co, Cu, Mg, Mn and Se levels were found to be significantly lower in the pre-eclamptic group compared to the normotensive group (p<0.05). This study confirms the association between pre-eclampsia and maternal trace as well as macro element levels.

Morphometrical analysis of placental functional efficiency in normotensive versus preeclamptic South African black women.

OBJECTIVE: To assess the umbilical cord centrality, placental morphometrics, and functional efficiency in preeclampsia. METHODS: Placental morphometry of normotensive (n = 69) and preeclamptic (n = 69) patients was evaluated. RESULTS: There was a significant reduction in mean placental surface area (p = 0.0001), length (p = 0.0001), thickness (p = 0.016), and volume (p = 0.0001) in the preeclamptic than in the normotensive groups. Umbilical cord insertion was predominantly eccentric with marginal in early (29%) and late-onset preeclampsia (16%). Placental and birth weight was lower (p = 0.0001) in preeclampsia than in the normotensive group. Placental efficiency was reduced in early-onset preeclampsia. CONCLUSION: This study demonstrates reduced placental morphometrics with impaired placental efficiency in preeclampsia.

Activation of CD35 and CD55 in HIV associated normal and pre-eclamptic pregnant women.

OBJECTIVE: The delicate balance which exists between complement activation and its regulation is altered in HIV infection and pregnancy disorders such as pre-eclampsia. Therefore, the purpose of this study was to investigate the expression of complement regulatory (Creg) proteins (CD35 and CD55) in HIV associated normal and pre-eclamptic pregnancies. STUDY DESIGN: The total study population (n=100) consisted of normotensive pregnant (n=50) and pre-eclamptic (n=50) women. These groups were equally sub-stratified into HIV infected and uninfected groups (n=25 per group). Standard haematological tests were conducted. Flow cytometric analysis of isolated neutrophils were performed using fluorescein isothiocyanate-conjugated anti-CD35 and phycoerythrin-cyanine 5 conjugated anti-CD55. RESULTS: HELLP syndrome characteristics of increased lactate dehydrogenase enzymes levels, low platelet counts, cell morphological abnormalities (red cell fragmentation) and anaemia were observed in 40% of the HIV infected pre-eclamptic group. Red cell fragmentation inclusive of burr cells and schistocytes were also noted. Activated partial thromboplastin time and fibrinogen differed significantly between the HIV uninfected pre-eclamptic compared to the HIV infected pre-eclamptic groups (p<0.01). Irrespective of HIV status, the mean fluorescence intensity of CD35 and CD55 were significantly higher in the pre-eclamptic compared to the normotensive pregnant (p=0.0001; p=0.0001 respectively) groups. In the pre-eclamptic groups, the expression of both CD35 and CD55 did not significantly differ between HIV infected and uninfected women (p=0.486; p=0.767 respectively). CONCLUSIONS: This study demonstrates an up-regulation of complement regulatory proteins, CD35 and CD55 in HIV associated pre-eclamptic compared to normotensive pregnancy. This elevation of the Creg proteins is an adaptive immune response to the high complement-mediated cell lysis that occurs in HIV infection and further aggravated by the complement activated state of pre-eclampsia.

Drug management of hypertensive disorders of pregnancy.

Drugs used in the acute and long-term management of hypertension in pregnancy and the preeclampsia-eclampsia syndrome have been reviewed and their therapeutic effects and maternal and fetal adverse effects have been considered. The review also focuses on recent developments in the areas of prevention and management of pre-eclampsia-eclampsia syndrome. Although a number of new drugs have emerged, as potentially useful in the management of hypertension in pregnancy and pre-eclampsia-eclampsia syndrome, some remain at the cornerstone of therapy; for example, methyldopa for long-term treatment of chronic hypertension, hydralazine or nifedipine for rapid reduction of severely elevated blood pressure, and magnesium sulphate for eclampsia. Some of these agents, especially the calcium antagonists, show promise in that their use is associated with fewer side effects. Safety for the fetus, however, has not been adequately evaluated yet. Neither aspirin nor calcium supplements appear to improve the outcome in pregnancy. Currently, the dilemma whether to treat hypertension in pregnancy and pre-eclampsia-eclampsia syndrome with old, established, cost-effective drugs or the promising newer drugs provides an interesting academic challenge.

Ultrastructure of Calymmatobacterium granulomatis: comparison of culture with tissue biopsy specimens.

The ultrastructural features of cells of Calymmatobacterium granulomatis from monocyte co-cultures and tissue biopsy specimens were compared. In cultures the bacteria were mainly extracellular, i.e., not within membrane-bound vacuoles. The bacterial body was surrounded by a uniformly extensive homogeneous layer with a relatively high electron density. This layer varied considerably in tissue biopsy specimens, having either homogeneously electron-dense or delicate web-like structures with varying density and thickness. In tissue specimens the bacteria were located predominantly within vacuoles of varying sizes in the cytoplasm of the macrophages and, occasionally, extracellularly within the intercellular spaces of the stroma. The bacterial cytoplasm contained ribosomes scattered throughout with electron-dense granules located peripherally. The trilaminar cell-wall structure was typical of a gram-negative organism, comprising an outer membrane, a middle electron-opaque layer and an inner plasma membrane. Surface structures such as fimbriae, flagella and bacteriophages were not identified in specimens from either source.