Optics and Imaging

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Morphometric comparisons of term placentae from normotensive and pre-eclamptic pregnancies suggest maladaptations of the fetal component of the placenta in pre-eclampsia.
(2012) Ducray, Jennifer Frances.; Naicker, Thajasvarie.
Adequate maternal, intervillous and fetal blood flow are all necessary for fetal wellbeing. Compromise to any part of this exchange would be detrimental to pregnancy outcome. Preeclampsia is associated with reduced maternal spiral artery flow, resulting in reduced placental perfusion. This in turn creates an ischemic environment which may pre-dispose morphological changes in placental villi. This pilot study utilized morphometric image analysis to examine some features of the fetal component of the placenta in normotensive (NT) and pre-eclamptic (PE) groups. The features examined included: density of placental villi (expressed as percentage of field area occupied by placental tissue); stem vessel carrying capacity (expressed as percentage of stem villus area occupied by vessel lumina); the thickness of the stem arterial walls relative to artery size (expressed as percentage of artery area occupied by arterial wall) and the extent of fibrosis associated with villi (expressed as percentage of field area occupied by fibrosis). The results were as follows: density of placental villus arrangement NT:51.89±6.19, PE:64.78±6.93 (P<0.001); carrying capacity of stem villi NT:17.20±11.78, PE:8.67±8.51 (P<0.001); relative thickness of stem villi arterial walls NT:74.08±12.92, PE: 86.85±10.55 (P<0.001); and extent of fibrosis NT:0.727±0.310, PE:1.582±0.707 (P<0.001). These significant differences between normotensive and pre-eclamptic placentae suggest possible fetal maladaptations in response to the intervillous ischemia, compounding the existing maternal compromise to materno-fetal exchange.
The spectrum of HIV related nephropathy in KwaZulu-Natal : a pathogenetic appraisal and impact of HAART.
(2012) Ramsuran, Duran.; Naicker, Thajasvarie.; Bhimma, Rajendra.
Sub-Saharan Africa bears 70% of the global HIV burden with KwaZulu-Natal (KZN) identified as the epicenter of this pandemic. HIV related nephropathy (HIVRN) exceeds any other causes of kidney diseases responsible for end stage renal disease, and has been increasingly recognized as a significant cause of morbidity and mortality. There is nonetheless a general lack of surveillance and reporting for HIVRN exists in this geographical region. Consequentially, the aim of this study was to outline the histopathogical spectrum of HIVRN within KZN. Moreover, from a pathology standpoint, it is important to address whether HIVRN was a direct consequence of viral infection of the renal parenchyma or is it a secondary consequence of systemic infection. Additionally, an evaluation of the efficacy of Highly Active Anti-Retroviral Therapy (HAART) in combination with angiotensin converting enzyme inhibitors (ACE-I) was performed via a genetic appraisal of localized replication of HIV-1 in the kidney, ultrastructural review and immunocytochemical expression of a podocyte maturity and proliferation marker pre and post-HAART. Blood and renal biopsies were obtained from 30 children with HIV related nephropathy pre- HAART, followed-up clinically for a period of 1 year. This cohort formed the post-HAART group. Clinical and demographic data were collated and histopathology, RT-PCR, sequencing, immunocytochemistry and transmission electron microscopy was performed. The commonest histopathological form of HIVRN in children (n = 30) in KZN was classical focal segmental glomerular sclerosis (FSGS) presented in 13(43.33%); mesangial hypercellularity 10(30%); mesangial, HIV associated nephropathy 3(11%) and minimal change disease 2(6.67%). Post-HAART (n = 9) the predominant pathology was mesangial hypercellularity 5(55.56%); FSGS 3(33.33%) and sclerosing glomerulopathy 1(11.11%). This study also provides data on the efficacy of HAART combined with ACE-I. The immunostaining pattern of synaptopodin, Ki67 and p24 within the glomerulus expressed as a mean field area percentage was significantly downregulated in the pre-HAART compared to the post-HAART group respectively (1.14 vs. 4.47%, p = 0.0068; 1.01 vs.4.68, p < 0.001; 4.5% vs 1.4%, p = 0.0035). The ultrastructural assessment of all biopsies conformed to their pathological appraisal however, features consistent with viral insult were observed. Latent HIV reservoirs were observed within the podocyte cytoplasm but was absent in mesangial or endothelial cells. Real-Time polymerase chain reaction assays provided evidence of HIV-1 within the kidney. Sequence analysis of the C2-C5 region of HIV-1 env revealed viral diversity between renal tissue to blood. In contrast to a collapsing type of FSGS that occurs in adults, the spectrum of paediatric nephropathy in treatment-naive children within KwaZulu-Natal was FSGS with mesangial hypercellularity. Additionally, our study demonstrates podocyte phenotype dysregulation pre- HAART and reconstitution post therapy. Evidence of ultrastructural viral reservoirs within epithelial cells is supported by a genetic appraisal confirming the ubiquitous presence of HIV DNA in renal tissue. Moreover, sequence analysis showed viral evolution and compartmentalization between renal viral reservoirs to blood. Finally, the interplay of viral genes and host response, influenced by genetic background, may contribute to the variable manifestations of HIV-1 infection in the kidney in our paediatric population.
The role of soluble FMS-like tyrosine-kinase-1, vascular endothelial growth factor and placental growth factor in HIV associated pre-eclamptic pregnancies : a South African perspective.
(2013) Govender, Nalini.; Naicker, Thajasvarie.
Introduction and aims. South Africa is the epicenter of the HIV/AIDS pandemic. Hypertensive disorders of pregnancy (15.7%) are the second cause of maternal deaths of which pre-eclampsia represents 83%. Normal pregnancy requires a balance between pro- and anti-angiogenic factors to necessitate effective vasculogenesis, angiogenesis and placental development, however, pre-eclampsia is characterised by an excess anti-angiogenic state. The hypoxic placenta releases excess anti-angiogenic factors into the maternal circulation causing endothelial dysfunction. However, there is no data to verify if HIV infection affects pre-eclampsia, or if the angiogenic imbalance is affected. Contradictory data exists on the association between HIV infection and pre-eclampsia. In an attempt to assess the role of HIV infection in pre-eclampsia, this study examined the immunolocalisation of sFlt-1, sEng, PlGF and VEGF in placentae of HIV negative and positive normotensive and pre-eclamptic pregnancies at term using immunohistochemistry (IHC) and immunoelectron microscopy (IEM). Additionally, we estimated the placental expression of sFlt-1, sEng, PlGF and VEGF to verify if the HIV negative differed from the HIV positive cohorts. We further evaluated the maternal serum to determine if variations existed in the circulating levels of these factors in HIV negative and positive normotensive and pre-eclamptic pregnancies. Methods. Following institutional ethical approval and informed consent, placental biopsies and maternal serum were collected post-delivery. For IHC and IEM, 130 and 25 placentae were evaluated, respectively. Following conventional immunohistochemical processing, 5μm sections were immunostained & immunoexpression of the various antibodies were evaluated with the Zeiss Axioscope A1 interfaced with an AxioVision Image analysis software package (version 4.8.3) in combination with the auto-measurement module (Carl Zeiss, Germany). Post-conventional immunoelectron processing, ultra-thin sections were immunolabelled. Sections were post-fixed, contrast enhanced with uranyl acetate and Reynolds lead citrate and viewed on a Jeol 1011 Transmission Electron Microscope. Additionally, the placental expressions of these factors were assessed using RT-PCR. In an attempt to confirm if maternal circulating levels of these factors differed, we quantitatively evaluated these factors in serum from HIV negative normotensives, HIV negative pre-eclamptics, HIV positive normotensives, and HIV positive pre-eclamptics using ELISA techniques. Results and Discussion. The expression of sFlt-1, sEng, PlGF and VEGF was confirmed using immunohistochemistry, RT-PCR and ELISAs. Irrespective of the HIV status, sFlt-1 and sEng was elevated with the concomitant reduction in PlGF in pre-eclamptic compared to normotensive pregnancies. The levels of VEGF were however undetectable across all study groups. It is plausible that this lack of effect of HIV status on the factors under study may be attributed to the treatment regimen as HAART is known to restore the immune response of HIV positive preeclamptic women. However, a concise anti-retroviral treatment history in our study was unavailable. Additionally, this study is novel in that it ultrastructurally immunolocalises sFlt-1, sEng, PlGF and VEGF within the placenta. This immunoelectron localisation data corresponds to our immunohistochemical data. Our study further demonstrates strong immunoreactivity of both placental sFlt-1 and sEng in pre-eclampsia with concurrent elevations in the maternal circulation. A qualitative increase in the occurrence of syncytial knots in the pre-eclamptics compared to the normotensive pregnancies was noted. These observations support the detachment of antixxx angiogenic rich microparticles from syncytial knots in the pre-eclamptics compared to the normotensive pregnancies was noted. These observations support the detachment of antiangiogenic rich microparticles from syncytial knots and their subsequent deportation and elevation in the maternal circulation. Moreover, their consequent antagonistic effects on VEGF, PlGF and TGF-β, disrupts the vascular endothelial maintenance. The strong immunoreactivity of sFlt-1, sEng, PlGF and VEGF was observed in villous endothelial cells. Moreover, a strong sFlt-1 and sEng but a weak PlGF and VEGF immunoreactivity was noted in syncytio- and cytotrophoblasts. This immunoexpression within trophoblasts is suggestive of their autocrine mode of action on normal trophoblast functions including invasion, differentiation and production. It is plausible that the angiogenic imbalance observed in our study, will impact on placental function, by modifying trophoblast activity thereby contributing to abnormal placentation. Conclusion. Our study supports the hypothesis that pre-eclampsia is characterized by an imbalance between pro- and anti-angiogenic factors. Whether the pregnancy is complicated by immune insufficiencies or not, does not affect the role of the anti-angiogenic factors in pre-eclampsia development. Nevertheless, the neutralising effect of HIV infection on the immune system may be insufficient in the development of pre-eclampsia. To our knowledge, the quantification of serum pro-/anti-angiogenic factors in HIV-associated pre-eclampsia is novel. In conclusion, our data reinforces the hypothesis that increased concentrations of sFlt-1 and sEng are involved in the pathogenesis of pre-eclampsia and indicates their possible use as discriminatory factors between diseases.
The role of leptin in HIV associated pre-eclampsia.
(2013) Haffejee, Firoza.; Naicker, Thajasvarie.; Singh, Moganavelli.
HIV and hypertensive disorders in pregnancy, in particular pre-eclampsia, are the main causes of maternal mortality in South Africa. In HIV associated pre-eclampsia, it is biologically plausible that the immune activation associated with pre-eclampsia may be neutralised by the immune suppression of HIV infection. The precise aetiology of pre-eclampsia is unknown, however leptin has been implicated in its development. Leptin is an adipocyte hormone, also produced by the placenta. It has a role in the development of inflammation. Adipose tissue is reduced in HIV infected individuals, resulting in lower leptin levels with consequent impaired immune function. This study aimed to compare serum and placental leptin levels in HIV infected and uninfected normotensive and pre-eclamptic pregnancies. Since insulin levels may affect the secretion of leptin, the study also compared insulin levels in these pregnancies. Following ethical clearance and hospital permission, 180 participants were recruited during their antenatal period. The groups were HIV- normotensive (n = 30), HIV+ normotensive (n = 60), HIV– pre-eclamptic (n = 30) and HIV+ pre-eclamptic (n = 60). Blood samples were collected ante-natally and placental samples post delivery. Serum leptin and insulin levels were determined by ELISA. Placental leptin levels were determined by ELISA and immunohistochemistry with morphometric image analysis. The placental production of leptin was determined by RT PCR. There was a non-significant increase in serum leptin levels in HIV- pre-eclampsia compared to HIV- normotensive pregnancies (p = 0.42). However leptin was decreased significantly in HIV+ pre-eclampsia compared to HIV- normotensive (p = 0.03). Based on HIV status leptin levels were decreased in HIV+ groups compared to HIV- groups in both pre-eclamptic (p < 0.01) and normotensive pregnancies (p < 0.01). Insulin levels of the HIV positive groups were lower than those of the HIV negative groups (p < 0.001). Insulin levels were also decreased in pre-eclampsia compared to normotensive pregnancies, irrespective of HIV status (p = 0.02). Immunohistochemistry demonstrated an increase in immuno-reactivity of leptin in the exchange villi of pre-eclamptic compared to normotensive placentae, irrespective of HIV status (p < 0.001). Supporting this finding, ELISA also demonstrated elevated leptin levels in the placenta of pre-eclamptic compared to normotensive pregnancies (p < 0.001). Placental leptin levels were similar in both HIV positive and negative pregnancies (p = 0.36). However, the placental leptin mRNA expression was up-regulated in HIV negative pre-eclampsia (p = 0.04) but not in HIV positive pre-eclampsia (p = 1.00). In conclusion, the elevated placental leptin in pre-eclampsia, irrespective of HIV status, is consistent with hypoxia. These elevated levels are not reflected in the maternal serum which raises the possibility of decreased leptin expression by adipose tissue especially in HIV infection where serum leptin levels are decreased. This would negate the increased placental leptin expression in pre-eclampsia. Furthermore, the elevated placental leptin levels are suggestive of an autocrine role of leptin in the placenta.
The role of peripheral natural killer cells in immunocompromised pre-eclamptic and normotensive pregnant black South Africans.
(2015) Ajith, Anushka.; Naicker, Thajasvarie.; Moodley, Jagidesa.
Abstract available in PDF file.
The role of trophoblast cells in HIV-1 passage across the placenta.
(2015) Dorsamy, Vinogrin.; Naicker, Thajasvarie.; Moodley, Jagidesa.
Background The combination of pre-eclampsia and human immunodeficiency virus (HIV) remains a major obstetric dilemma in South Africa and, consequently, mother to child transmission of HIV remains a burden in our community. The human placenta is in direct contact with maternal blood and is therefore susceptible to HIV infection or transmission. Cluster of differentiation (CD) 4 (CD4) and C-C chemokine receptor type 5 (CCR5 or CD195) are known to be important receptors for HIV transmission. Maternal in utero transmission is thought to mainly rely on R5-trophic viruses. Intercellular adhesion molecule 2 (ICAM-2 or CD102) is a member of intercellular receptor family found on endothelium and leucocytes that is involved in cell mediated immune recruitment. ICAM-2 is implicated in HIV transmission. The aim of this study was to immunohistochemically localise HIV (p24 viral core) and the HIV receptor (CD4) within the placenta of HIV associated pre-eclamptic pregnancies to elicit the mechanism of vertical transmission of HIV. A further aim was to immuno-localise the HIV co-receptor (CCR5) and ICAM-2 within these placentae. Method Post institutional ethics approval, a retrospective cohort of 80 out 180 archived paraffin embedded placental blocks was sourced from mothers who delivered at Prince Mshiyeni Memorial district hospital in KwaZulu-Natal. Four groups (n=20/group) were categorised according to pregnancy status (normotensive and pre-eclamptic) and HIV status (positive and negative). Pre-eclampsia was defined as new onset hypertension (≥140/90mmHg) with proteinuria. Immunohistochemistry was performed using the Envision kit (DAKO, Denmark). Anti-human mouse CD4, and p24 antibodies were used to identify presence of HIV and CD4 receptors. The antihuman mouse antibodies CCR5 and ICAM-2 were used to detect these receptors within placentae. An Axiovision A1 light microscope and Axiovision (Zeiss) software was used for image acquisition and analysis where percentage staining in microns per field area (20x objective) was measured. Results Eight out of 180 HIV positive mothers in both pre-eclampsia and normotensive groups transmitted HIV to their babies (4%) despite receiving antiretroviral therapy. CD4 positive maternal immune cells and endothelial cells lining fetal vessels were found. CD4 was very rarely seen on syncytiotrophoblast. p24, however, was present in both the maternal and fetal blood circulation, as well as within Hofbauer cells. CCR5 showed diffuse staining of all exchange villi within all four cohorts. A factorial univariate ANOVA was then performed and both HIV and pregnancy status had a significant main effect on expression of CCR5 in placental tissue. There was greater expression of CCR5 in the HIV positive groups compared to the HIV negative groups [F (1,169) =6.979, p=0.009] and the pre-eclamptic compared to the normotensive groups [F (1,169) =8.803, p=0.003]. ICAM-2 was sparse and found in areas around syncytial knots as well as lining an arterial supply in a stem villus. An independent samples Mann-Whitney U test showed a significant difference in the distribution of ICAM-2 expression between the pre-eclamptic and normotensive groups (p<0.001) and the HIV positive groups. The HIV negative pre-eclamptic group showed the greatest expression of ICAM-2 compared to the 3 other groups. Discussion and Conclusion The immunolocalisation of p24 provides evidence of HIV successfully traversing the fetomaternal barrier. Interestingly, HIV was found to be present in the placentas of babies that were HIV positive as well as those who were HIV negative 6 weeks later. This suggests an unknown mechanism that protects the fetus from viral insult. All receptors and co-receptors used for HIV infection are found on the trophoblast, suggesting that this barrier is susceptible to HIV infection. Pre-eclampsia increases expression of both cytokine receptors and inflammatory markers which may increase susceptibility to infection. Further ultrastructural and biomolecular work to identify the immune cells and expression of receptors involved will corroborate our findings.
Trace element analysis of biological samples from normotensive and pre-eclamptic South African pregnant women.
(2016) Soobramoney, Cassandra.; Naicker, Thajasvarie.; Maduray, Kaminee.; Moodley, Jagidesa.
Abstract available in PDF file.
The effect of adipokines in HIV associated pre-eclampsia : (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon like peptide-1, glucagon, insulin plasminogen activator inhibitor-1 and visfatin).
(2016) Mathonsi, Colisile N.; Moodley, Jagidesa.; Naicker, Thajasvarie.; Ajith, Anushka.
Introduction: South Africa has a maternal ratio of 300 deaths/100,000 live births. Non-pregnancy related infections (mainly deaths in HIV infected pregnant women complicated by tuberculosis and pneumonia) accounts for 34.7% of maternal deaths followed by obstetric haemorrhage and hypertension accounts (15.8% and 14.8% respectively). Moreover, 61% of women South Africa is overweight or obese (almost double the global rate of 30%). In pregnancy, endocrine and metabolic maternal adaptations include increase in body weight, however, the impact of adipokines in HIV associated pre-eclampsia remains unknown. The aim of the study was to examine the levels of adipokines viz., C-peptide, ghrelin, gastric inhibitory polypeptide (GIP), glucagon like peptide 1 (GLP), plasminogen activator inhibitory (PAI) 1, visfatin, glucagon and insulin in HIV associated pre-eclampsia. Materials and Methods: Following institutional and regulatory approval, participants (n=301) were recruited from RK Khan Hospital and divided into groups non-pregnant (n=90), normotensive (n=121), early (n=32; EOPE) and late onset (n=58; LOPE) pre-eclampsia. The pregnant cohort was stratified according to their HIV status. Maternal clinical demographics, indications and mode of delivery were recorded. Serum was used to quantify the adipokines levels using the multiplex ELISA technique. Absorbance was read spectrophotometrically at 450 nm. Graph Pad Prism (version 6) was used to analyse all data. Result: C-peptide did not differ according to HIV status. With regards pregnancy type, there was a significant difference in c-peptide between the non-pregnant versus normotensive pregnant (p<0.01) and the normotensive versus LOPE groups (p<0.01) being elevated both the pre-eclamptic groups (EOPE +LOPE). Ghrelin did not differ across study groups (p>0.05), by HIV status (p>0.05). When considering HIV status, GIP varied between positive and negative groups (p<0.001). Additionally, there was a significant difference in GIP between the non-pregnant versus normotensive pregnant (p<0.01); normotensive pregnant versus EOPE (p<0.05) and the normotensive pregnant versus the LOPE group (p<0.01). GIP was elevated in the HIV positive EOPE group. Moreover, a significant difference in GLP-1 was noted across the study groups (p<0.05) and between non-pregnant versus normotensive groups (p<0.01). When considering HIV status, HIV positive groups differed from negative study groups (p<0.05). Additionally, the Mann Whitney U test showed a significant difference between the non-pregnant and the normotensive group (p<0.01). Glucagon-like peptide-1 was significant different across the study groups, with its levels elevated in the pre-eclamptic groups compared to the normotensive pregnant group (p<0.05), additionally, there was a difference between non-pregnant versus normotensive pregnant groups (p<0.01). Glucagon did not differ across the study groups (p>0.05), however, was significantly different between the non-pregnant and normotensive group (p<0.05). HIV status did not affect glucagon levels (p>0.05). A significant difference between HIV positive non-pregnant and HIV negative non-pregnant was noted (p<0.05). Insulin was not significantly different across the study groups (p>0.05) and by HIV status (p>0.05). However, a significant difference between the non-pregnant versus normotensive group (p<0.05) was noted. PAI-1 did not differ across the study groups (p>0.05) and between the groups (p>0.05). PAI-1 did not differ according to HIV status (p>0.05). A significant difference in visfatin across the study groups (p<0.05) and between the non-pregnant versus normotensive pregnant group (p<0.05) and the late onset pre-eclamptic versus the non-pregnant group (p<0.01) was observed. There was no effect of HIV status on the level of visfatin across the study groups (p<0.05). There was a significant difference between the HIV positive versus negative non-pregnant groups (p<0.05), furthermore, we have observed low levels of visfatin in the HIV positive pre-eclamptic groups. Discussion and conclusion: This study demonstrates elevated c-peptide, GIP, GLP-1, Insulin, PAI-1 and Visfatin in the pre-eclamptic groups compared to normotensive pregnant groups. These adipokines play a role in glucose homeostasis and have been reported to play a role in development of insulin resistance which is a high risk factor for developing pre-eclampsia. Several studies have reported that adipose tissue derived hormones, play a crucial role in the pathogenesis or as risk factors of pre-eclampsia development. Additionally, it is reported that adipokines are elevated in people with higher BMI (obese and overweight) which in turn predisposes one for developing pre-eclampsia. In terms of HIV status, we have observed that many of the adipokines were elevated in the HIV positive compared to the HIV negative group. This correlates with studies which reported that HIV plays a role in dysregulation of adipokines. In conclusion, our study is the first to examine adipokine dysregulation in the triad of HIV infection, pre-eclampsia and obesity. Furthermore, we have established that adipokines: C-peptide, GIP, GLP-1, PAI-1 and visfatin were significantly dysregulated hence they may have predictor test value in diagnosing pre-eclampsia development.
The role of CD69 in HIV-associated pre-eclamptic and normotensive pregnant black South Africans.
(2016) Zulu, Nomfundo Nokuthula Simlindile.; Ajith, Anushka.; Naicker, Thajasvarie.; Moodley, Jagidesa.
Abstract available in PDF file.
Role of biomakers, kidney injury molecule-1, interleukin-18, calbindin and monocyte chemotactic protein-1, in evaluating and diagnosing kidney injuyr in pre-eclampsia.
(2016) Eltounali, Soumaya.; Naicker, Thajasvarie.
Abstract available in PDF file.
The role of pro-renin and its receptor expression in pre-eclampsia complicated by HIV infection.
(2016) Silwane, Londiwe N. B.; Naicker, Thajasvarie.; Ajith, Anushka.
Abstract available in PDF file.
The role of macrophages, dendritic and Langerhans cells in the mother to child transmission of HIV in placental tissue of normotensive pregnancies.
(2016) Vallen, Camille J.; Naicker, Thajasvarie.; Dorsamy, Vinogrin.
Abstract available in PDF file.
The role of platelet endothelial cell adhesion molecule-1 (Pecam-1) and soluble vascular endothelial growth factor recepror (sVEGFR)-1 and -2 in the pathogenesis of HIV associated pre-eclampsia.
(2016) Thakoordeen, Semone.; Naicker, Thajasvarie.
Abstract available in PDF file.
The role of c-jun n-terminal kinase (JNK) and tumour protein (p53) in HIV associated pre-eclampsia.
(2017) Pillay, Yazira.; Naicker, Thajasvarie.
Background: In pre-eclampsia, immune maladaptation to the foetal allograft results in impaired trophoblast invasion and defective spiral arterial remodelling with consequential placental oxidative stress. Placental apoptosis can be initiated by various stimuli including hypoxia and oxidative stress and is notably exaggerated in pre-eclampsia. This elevated apoptosis prevents normal replenishment of the syncytiotrophoblast, promotes syncytial degeneration and releases vasoactive or inflammatory factors into the maternal circulation thereby provoking the endothelial dysfunction seen in pre-eclampsia. Since the p53 antigen and JNK are important mediators of apoptosis we determined their expression in HIV associated pre-eclampsia. Method: Blood samples were collected from normotensive pregnant and pre-eclamptic HIV infected and negative women. Buffy coat was extracted and a Bio-plex multiplex assay to quantify expression of phosphorylated-p53 and JNK. Results: Based on pregnancy type, a significant difference in the expression of p53 was noted between the pre-eclamptic vs normotensive pregnant group regardless of HIV status (p=0.0162). Irrespective of pregnancy type, there was also a significant difference found between the HIV positive and HIV negative groups (p=0.0469). Furthermore, there was a significant difference in the expression of p53 between the HIV negative pre-eclamptic vs the HIV negative normotensive group and HIV infected normotensive vs the HIV negative pre-eclamptic group. Despite having no statistical significance (p=0.8701), the expression of JNK was found to be increased in the pre-eclamptic compared to the normotensive pregnant group. Similarly, based on HIV status, regardless of pregnancy type no statistical significance was found (p=0.2227), however, there was a decrease in the expression of JNK in the HIV positive compared to the HIV negative group. xiii Conclusion: These experiments demonstrate a significant increase in the expression of p53 with an upwards trend in the expression of JNK in pre-eclampsia, confirming their influence on trophoblast cell invasion in pre-eclampsia development. This increase in expression of p53 and JNK in pre-eclampsia, holds potential value as a risk indicator of pre-eclamptic development. In contrast, a significant down regulation of p53 with a downwards trend of JNK expression was noted in the HIV positive group, possibly due to immune reconstitution following HAART.
Cell signaling expression of stat-3 and mek-1 in HIV-associated pre-eclampsia.
(2017) Padayachee, Sayuri.; Naicker, Thajasvarie.
Background: Sub-Saharan Africa remains the epicenter of the HIV pandemic. In South Africa 35.8% of maternal deaths are ascribed to non-pregnancy related infections, namely HIV infection. The prevalence rate of HIV in pregnancy in KwaZulu-Natal is an estimated 37.7%. Furthermore, in women of reproductive age, the incidence of HIV infection is high (18.8%). The shallow trophoblast invasion and the lack of physiological conversion of the spiral arteries into small bore low resistance conduits is the primary cause behind the pathogenesis of pre-eclampsia. HIV-positive patients on HAART are predisposed to pre-eclampsia development. Trophoblast cells are stimulated to invade the maternal decidua by interacting cytokines and growth factors in the local environment through signal transduction pathways. Aberrant cell signaling and signaling molecule function impedes trophoblast invasion necessary for a healthy pregnancy, leading to endothelial dysfunction. As a result, the expression of cell signaling analytes may potentially be a predictive biomarker for patients at risk to pre-eclamptic development. This study investigated expression of STAT-3 and MEK-1 in HIV-associated pre-eclampsia, as a diagnostic tool of abnormal placentation in pre-eclampsia. Method: Venous blood samples of 40 normotensive and 40 pre-eclamptic patients further stratified by HIV status were collected at a large regional hospital for buffy coat extraction, followed by analysis of cell signalling analytes by the Bio-Plex Multiplex immunoassay. Results: The downregulation of both STAT-3 and MEK-1 expression was observed in pre-eclamptic pregnancies irrespective of HIV status, respectively (p < 0.05; p = 0.1526). No significance for STAT-3 (p = 0.0859) was detected between HIV-positive and HIV-negative groups irrespective of pregnancy type, although a lowered trend was observed in the HIV-positive group. Contrary to expected outcomes, MEK-1 expression was significantly decreased (p = 0.0102) in the HIV-positive group, irrespective of pregnancy type. Conclusion: This study demonstrated the downregulation of STAT-3 and MEK-1 expression in pre-eclampsia, corroborating a defective trophoblast invasion. The decreased expression of STAT-3 in HIV-infection may be attributed to HAART and/or to the reduced expression of IL-6 that stimulates STAT-3 phosphorylation. It is also plausible to assume that the downregulation of MEK-1 arises from non-phosphorylation of HIV-regulatory proteins. Additional studies, are required to further investigate the role of signal transduction pathways and its effect on HAART in pre-eclampsia development.
The role of albumin, β₂M and Cystatin C as urinary biomarkers in idopathic and HIV-associated focal segmental glomerulosclerosis in children.
(2017) Persadh, Kalindi.; Naicker, Thajasvarie.; Bhimma, Rajendra.
Abstract available in PDF file.
Expression of plasma nuclear factor KAPPA-B (NFκB) and inhibitory subunit KAPPA B ALPHA (IκB-α) in HIV-associated pre-eclamsia.
(2017) Zozo, Bambanani Selunathi.; Naicker, Thajasvarie.
Objective: The relationship between pre-eclampsia and HIV-1 infection is one of the most unexplored relationships in research. Pre-eclampsia is characterized by inflammation and HIV is characterized by a decline in immune activity. The NFκB pathway is involved in pre-eclampsia and in HIV-1 infection as a transcriptional factor in both conditions. Previous literature has showed that NFκB is upregulated in both pre-eclampsia and HIV-1 infection. Therefore, the aim of this study was to investigate the level of plasma NFκB and the inhibitory subunit IκB-α in HIV associated pre-eclampsia. Method: This retrospective study examined plasma NFκB and IκB-α expression in normotensive (n =32) and preeclamptic (n = 34) HIV positive and HIV negative pregnant women. Quantification of plasma NFκB and IκB-α expression were done using a Bio-Plex Multiplex immunoassay. Results: Our results demonstrated a significant decrease in the level of plasma NFκB expression in pre-eclamptic compared to normotensive pregnancies (p< 0.05), irrespective of HIV status. However, the level of plasma NFκB expression was not significantly different between HIV positive and HIV negative women, irrespective of pregnancy type. Moreover, a significant difference in NFκB expression across all the study groups was observed, specifically a significant decrease in NFκB expression in HIV positive pre-eclamptic women compared to normotensive women (p < 0.05). Furthermore, based on pregnancy type, a significant decrease in the level of plasma IκB-α expression was noted in pre-eclamptic compared to normotensive pregnancies, irrespective of HIV status (p< 0.05). However, our results showed no significant difference across all groups. Although no significance was xii observed, a downwards trend in plasma IκB-α expression was observed in HIV positive pre-eclamptic compared to normotensive women. Conclusion: Our study demonstrates decreased plasma NFκB and IκB-α expression in preeclamptic women irrespective of HIV status. This could be attributed to oxidative stress as an underlying factor subsequently leading to decreased plasma NFκB and IκB-α in preeclamptic women. HIV status had no effect on Plasma NFκB and IκB-α expression. The similarity in plasma NFκB and IκB-α expression based on HIV status may be due to antiretroviral therapy.
The role of primigravidae, lymphatic vessel endothelial receptor-1 and podoplanin in HIV associated early and late onset pre-eclampsia.
(2017) Onyangunga, Onankoy Atshakala.; Naicker, Thajasvarie.; Moodley, Jagidesa.
Abstract available in PDF file.
The role of C- reactive protein and serum amyloid A in HIV associated pre-eclampsia.
(2018) Sikutshwa, Akhona.; Naicker, Thajasvarie.
Abstract available in PDF file.
The role of basic fibroblast growth factor in HIV associated preeclampsia.
(2018) Sangany, Charline Mukasa.; Naicker, Thajasvarie.
Background: In South Africa, hepatitis B virus (HBV) infection remains a major cause of morbidity and mortality, however, little is known about the prevalence and distribution of HBV in some regions and populations. Methods: This secondary analysis is based on 9791 participants (15-49 years old) enrolled in the HIV incidence Provincial Surveillance System (HIPSS); a population-based household study undertaken from June 2014 to June 2015 in the Vulindlela (rural) and Greater Edendale (periurban) areas of the uMgungundlovu district, KwaZulu-Natal (KZN), South Africa. Interviewer administered questionnaires were completed to obtain demographic, psychosocial, behavioural and clinical information. Peripheral blood samples were collected and sera were tested for hepatitis B surface antigen (HBsAg) and all samples testing positive were further tested for hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe). The estimated weighted seroprevalence of HBV markers was calculated and the association of HBsAg with sociodemographic and behavioural factors measured. Results: The overall HBsAg prevalence was 4.0% (95% confidence interval (CI) 3.4-4.5); 4.8% (95% CI 3.8- 5.8) in men and 3.2% (95% CI 2.5-3.9) in women, P=0.01. Among HBsAg positive participants, 35.2% (95% CI 29.2-41.2) were HBeAg positive and 66.3% (95% CI 60.1-72.4) were anti-HBe positive. Among men 15-19 years old HBeAg seroprevalence was 92.2% (95% CI 75.8-100) compared to 4.4% (95% CI 0-13.7) in women in the same age group; P <0.01. HBsAg prevalence was 6.4% (95% CI 5.3-7.5) among HIV positive participants compared to 2.6% (95% CI 1.9-3.2) among HIV negative participants, (P<0.01) and was higher among HIV positive men 8.7% (95% CI 6.3-11.2) compared to HIV positive women 5.0% (95% CI 3.8-6.2), P<0.01. Conclusion: HBV infection, particularly among HIV positive men remains an important public health problem in rural and periurban communities in KwaZulu-Natal, South Africa. The prevalence of HBsAg and HBeAg highlight the importance of surveillance and an important missed opportunity for the scale up of programmes to achieve the goal of controlling HBV for public health benefit.

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