Masters Degrees (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 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.
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 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 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.
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 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.
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.
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.
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 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 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 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.
Hepatocyte growth factor and epidermal growth factor in HIV associated preeclampsia.
(2018) Kupsamy, Kyle.; Naicker, Thajasvarie.
Background: The survival or death of a cell is reliant upon growth factors. Hepatocyte and Epidermal Growth Factor (HGF and EGF) promote vital cellular processes such as cell survival, proliferation, differentiation, growth, invasion and repair via various pathways. Hence these growth factors facilitate normal pregnancy. In complications such as preeclampsia (PE), decreased trophoblast invasion results in defective spiral artery remodeling, which leads to decreased blood flow and a hypoxic micro-environment. In South Africa (SA), HIV infection and PE are the leading causes of maternal mortality and morbidity. In light of the high prevalence of HIV infection and PE in SA, this study aimed to determine the concentrations of HGF and EGF in HIV associated PE. Methods: Post ethics approval, serum samples were collected from normotensive HIV-negative (n = 20); normotensive HIV-positive (n = 20); preeclamptic HIV-negative (n = 20) and preeclamptic HIV-positive (n = 20) women. All HIV-positive women received Highly Active Anti-Retroviral Treatment (HAART). Quantification and analysis of HGF and EGF expression was attained by using the Bio-Plex multiplex immunoassay technique. Results: As expected there was a statistically significant difference between gestational age, systolic and diastolic blood pressures across the study groups (p<0.0001). No significant difference was noted in maternal age (p=0.16), parity (p=0.47) and maternal weight (p=0.36) across all study groups. Irrespective of pregnancy type, HGF was significantly increased in HIV-positive women vs HIV-negative women (p=0.0225). However, no statistical significance was found based on pregnancy type (p=0.8890). A significant decrease of HGF expression was noted between normotensive HIV-negative and normotensive HIV-positive women (p=0.0022). Irrespective of pregnancy type, EGF was found to be significantly elevated in HIV-positive compared to HIV-negative women (p=0.0055). In addition, preeclamptic women displayed a higher EGF level compared to normotensive women (p=0.003), regardless of HIV status. The Epidermal Growth Factor was significantly down-regulated in normotensive HIV-negative group vs normotensive HIV-positive (p<0.001), preeclamptic HIV-positive (p<0.001) and preeclamptic HIV-negative groups (p<0.001). Conclusion This novel study displays a significant up-regulation in the expression of HGF and EGF in HIV infection during pregnancy, reflecting an immune reconstitution following HAART. These findings may be caused due to the HIV accessory protein Tat that inhibits growth factor function thereby, negatively impacting cell migration. The up-regulation of EGF expression in PE, may be responsible for impaired trophoblast cell invasion. As anticipated in HIV associated PE, EGF expression increased in HIV infected pregnancies and PE. The expression Epidermal Growth Factor in HIV associated PE, may be used as a risk indicator, predicting PE development prior to the manifestations of clinical signs and symptoms.
The role of Endothelin-1 in HIV associated pre-eclampsia.
(2019) Mthembu, Mbuso Herald.; Naicker, Thajasvarie.
Introduction and Background: Preeclampsia (PE), a hypertensive disorder specific to human pregnancy, remains a major cause of maternal mortality and morbidity globally. Endothelin-1 (ET-1) is a powerful vasoconstrictor that plays a crucial role in endothelial cell dysfunction, a characteristic feature of preeclampsia development. As a result, this study assessed the role of ET-1 in an HIV-infected preeclamptic cohort. Ethics approval was obtained BCA/17. Method: The study population (n = 72) was grouped according to pregnancy type i.e., normotensive (n = 36) and preeclamptic (n = 36) further stratified by human immunodeficiency virus (HIV) status. ET-1 levels were quantified using the Bioplex Immunoassay. Results: Gravidity, gestational age, systolic and diastolic blood pressure were significant across the study groups (p < 0.05). The concentration of ET-1 was significantly elevated in preeclamptic vs normotensive pregnancies regardless of HIV status (p ≤ 0.0418). Conclusion: This study observed a non-significant increase in ET-1 in the HIV positive preeclampsia group compared to the HIV negative pre-eclampsia group. ET-1 was significantly increased in pre-eclampsia compared to normotensive pregnancy. Isendlalelo nesingeniso: I-preeclampsia (PE), isifo sokunyuka kokugijima kwegazi esihlasela umuntu wesifazane ngesikhathi ekhulelwa, iyimbangela enkulu yokushona kukamama kanye nokugula komzimba emhlabeni wonke jikelele. I-Endothelin-1 (ET-1) iyi-vasoconstrictor enamandla ebamba iqhaza elibalulekile ekungasebenzi kahle kwamaseli we-endothelial, ibuye ibe nomthelela ekuthuthukeni kwe Preeclampsia. Lolu cwaningo beluhlola iqhaza le-ET-1 kubantu besifazane abanegciwane lesandulela ngculaza Kanye ne Preeclampsia ngesikhathi esisodwa. Indlela yokwenza: Inani labantu abacwaninguyo lingama-72, lihlukaniswa ngokwamaqembu ezinhlobo zokukhulelwa i.e., i-Abangenaso isifo (Normatensive) abangama-36 kanye nabanesifo se Pre-eclampsia abangama-36-, abuye aphindwa yahlukaniswa ngesimo seegciwane lesandulela ngculaza. Amazinga we-ET-1 asehlaziywa ngokusebenzisa iBioplex Immunoassay. Imiphumela: Ukuthola amandla wobudala, iminyaka yokuthomba, umfutho wegazi ne-diastolic kubonakale kwenza umehluko kuwo amaqembu ocwaningo (p < 0.05). Amazinga we-ET-1 akhuphuke kakhulu ekukhulelweni kwe-PE uma kuqhathaniswa nokukhulelwa okujwayelekile kungakhathalekile ukuthi sinjani isimo segciwane lesandulelaNgculaza (p ≤ 0.0418). Isiphetho: Lolu cwaningo lubone ukwanda okungabalulekanga kwe-ET-1 eqenjini labanepreeclampsia Kanye negciwane lesandulela ngculaza kuqhathaniswa nabane Preeclampsiankodwa bengenalo igciwane lesandulela ngculaza. I-ET-1 ibonakale yanda kakhulu ekukhuliseni i-preeclampsia uma kuqhathaniswa nokukhulelwa okujwayelekile.
The role of Vascular Endothelial growth factor receptor-3 in the placenta in HIV associated preeclampsia.
(2019) Pillay, Saieshni.; Naicker, Thajasvarie.
Summary: PE and HIV dualism in pregnant HAART women are yet to be investigated. Furthermore, the effect on VEGFR-3 and subsequent downstream influence on angiogenesis is poorly understood. Therefore, this investigation evaluates the immuno-expression of VEGFR-3 in placental conducting and exchange villi from normotensive, preeclamptic and HIV+ African women, using morphometric image analysis. Study design: This is a prospective study utilizing retrospectively collected, paraffin wax-embedded, placental samples (n=90) that were immuno-stained for VEGFR-3. The study population consisted of normotensive (n=30) and pre-eclamptic (n=60) groups which were further stratified on the basis of HIV status (negative - and positive +), and early and late onset preeclampsia (EOPE and LOPE respectively). The final groups were as follows; N- (n=15), N+ (n=15), EOPE- (n=15), EOPE+ (n=15), LOPE- (n=15) and LOPE+ (n=15). Brightfield microscopy and morphometric image analysis of VEGFR-3 immuno-expression within conducting and exchange placental villi was performed. Results: HIV status analysis did not demonstrate a significant difference in VEGFR-3 immunostaining for both villous types. The N vs. PE comparative analysis showed a downregulated immuno-expression of VEGFR-3 in both conducting (p = 0.0107) and exchange (p < 0.0001) villi. Results from analysis of pregnancy subtypes showed a significant difference in VEGFR-3 expression between N vs. EOPE regardless of villous type. Conclusion: This study demonstrates that HIV infection does not significantly alter VEGFR-3 placental immuno-expression in pregnant women receiving HAART irrespective of pregnancy type. Furthermore, VEGFR-3 immuno-expression was dysregulated in EOPE women, irrespective of HIV status. These novel findings emphasize severe down-regulation of VEGFR-3 in preeclamptic women, and provide compelling evidence for a future investigation into placental angiogenic and lymphangiogenic regulation in the early onset of PE. Isifinyezo: Inhlanganyela yePE neHIV kwabesifazane abakhulelwe abemukela iHAART kusamele kuphenywe. Ngakho-ke, lolu phenyo luhlola ukubonakaliswa kwe-VEGFR-3 kwiplacental ekuqhubeni nasekushintshaniseni i-villi kusuka ku-normotensive, preeclamptic ne-HIV+ kwabesifazane abansundu, kusetshenziswa ukuhlaziywa kwezithombe. Umklamo wokutadisha: Lokhu kucwaninga okungenzeka kusetshenziswa amasampula eplacental aqoqiwe, afakwe kwi-paraffin wax (n=90) abegcinelwe i-immuno-stain for VEGFR-3. Inani labantu abacwaningwayo liqukethe amaqembu: i-Normotensive (n=30) kanye ne-pre-eclamptic (n = 60) abephinde ahlukaniswa ngesisekelo sesimo se-HIV (abangenayo i-HIV Kanye nabanayo i-HIV+), kanye nabaqalwa yi-preeclampsia nalabo abakhombisa i-preeclamsia emva kwesikhathi eside (i-EOPE ne-LOPE) ngokulandelana. ). Amaqembu esewonke ngokulandelayo; N- (n=15), N+ (n=15), EOPE- (n=15), EOPE+ (n=15), LOPE- (n=15) no-LOPE+ (n=15). IBrightfield microscopy nokuhlaziywa kwezithombe imorphometric yeVEGFR-3 nokuziveza kwayo ngokuqhuba nokushintshaniswa kweplacental villie kwenziwa. Imiphumela: Ukuhlaziywa kwesimo seHIV akuvezanga umehluko omkhulu kwiVEGFR-3 immuno-staining kuzo zombili izinhlobo zeVillous. Ukuhlaziywa kokuqhathaniswa kwe-N vs. PE kukhombise ukubonakaliswa okuphansi kwe-immuno-expression kwe-VEGFR-3 kokubili kuqhuba (p = 0.0107) kanye nokushintshaniswa (p < 0.0001) villi. Imiphumela yokuhlaziywa kwezinhlobo ezahlukene zokukhulelwa zikhombise omkhulu umehluko ekubonisweni kweVEGFR-3 phakathi kwe N iqhathaniswa neEOPE kungakhathaleleki uhlobo lwevillous. Isiphetho: Lomkamo ukhombisa ukuthi ukutheleleka nge HIV akunawo umthelela omkhulu ekuvimbeni iVEGFR-3 immuno-expression kwabesifazane abakhulelwe abemukela iHAART kungakhathalaleki uhlobo lokukhulelwa. Ngaphezu kwalokho, iVEGFR-3 immuno-expression kwabesifazane abaneEOPE ayisebenzanga, kungakhathaleki isimo sabo seHIV. Okutholakale emibhalweni lugcozelela ngokukhulu ukwehla kwezinga kweVEGFR-3 kwabesifazane aba-preeclamptic, futhi kunikeza ubufakazi obuqanda ikhanda obungasetshenziswa kucwaningo oluzayo kweplacental angiogenic nelymphangiogenic regulation kulabo abaqedwa yiPE.
The role of soluble e-selectin and thrombospondin-2 in HIV associated preeclampsia.
(2019) Naidoo, Girija.; Naicker, Thajasvarie.
Objective: HIV infection and hypertensive disorders of pregnancy are common causes of maternal mortality in South Africa. Preeclampsia (PE) is a pregnancy-specific disorder that contributes to the majority of maternal deaths caused by hypertension in pregnancy. Reduced placentation, endothelial dysfunction of multiple organs and inflammation occur during PE. Endothelial cells express the adhesion molecule soluble E-selectin (sE-selectin) in response to inflammation. This molecule facilitates the cohesion of leukocytes to endothelial cells. In PE, endothelial cell activation and dysfunction cause endothelial cells to secrete the glycoprotein thrombospondin-2 (TSP-2). TSP-2 affects cellular functions, plays a regulatory role in the extracellular matrix and is an inhibitor of angiogenesis. In PE, an imbalance of angiogenic and anti-angiogenic factors result in dysregulation of angiogenesis. Considering the high rate of maternal mortality in South Africa due to HIV infection and PE, the aim of this study was to investigate the role of sE-selectin and TSP-2 in HIV-associated preeclamptic and normotensive pregnancies. Method: The study population (n = 72) comprised of normotensive pregnant (n = 36) and preeclamptic (n = 36) groups. These groups were further stratified by HIV status (negative vs. positive). The Bio-Plex immunoassay technique was used to measure serum concentrations of sE-selectin and TSP-2. Results: There was a statistical difference observed in gestational age, systolic blood pressure, diastolic blood pressure and baby weight across the study groups (p < 0.0001). sE-selectin: Based on pregnancy type and HIV status, levels of serum sE-selectin were significantly increased in preeclamptic HIV-negative compared to normotensive HIV-negative groups (p = 0.0070). TSP-2: Regardless of HIV status and based on pregnancy type, TSP-2 levels were significantly elevated (p = 0.0429) in preeclamptic compared to normotensive groups. Based on HIV status, a significant upregulation (p = 0.0095) of TSP-2 was noted in HIV-positive compared to HIV-negative groups. Furthermore, based on pregnancy type and HIV status, levels of TSP-2 were statistically significant across all study groups (p = 0.0229). Conclusion: This study highlights the role of sE-selectin and TSP-2 in preeclamptic women compromised by HIV infection and demonstrates the potential biomarker value of sE-selectin and TSP-2 in the early diagnosis of preeclampsia.
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.
The regulation of sVEGFR-2 and sVEGFR-3 in the serum of pregnant women with HIV- related Pre-eclampsia recieving antiretroviral therapy.
(2020) Abel, Tashlen.; Naicker, Thajasvarie.
Background: An imbalance in the concentration of pro- and anti-angiogenic factors is evident in preeclampsia (PE). This study evaluated the expression of soluble vascular endothelial growth factor receptor 2 (sVEGFR-2) and sVEGFR-3 in the serum of preeclamptic compared to normotensive women complicated by Human Immunodeficiency Virus (HIV) infection. Additionally, in light of the coronavirus disease 2019 (COVID-19) pandemic, maternal and foetal health is a great concern; hence, we have composed a review article that provides an insight into the synergy of PE, HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, as well as the involvement of epigenetic regulation. Method: The serum expression of sVEGFR-2 and sVEGFR-3 in preeclamptic vs normotensive pregnancies, stratified by HIV status (n = 19) was evaluated through the utilization of a Milliplex Multiplex immunoassay. Results: In comparison to normotensive (HIV-negative and HIV-positive), gestational age (p = 0.0004), systolic and diastolic blood pressure (p<0.0001) , and parity (p = 0.0042) were significantly different in preeclamptic (HIV-negative and HIV-positive) pregnancies. The serum expression of sVEGR-2 was significantly downregulated in PE compared to normotensive pregnancies (p = 0.0025), regardless of HIV status. A downward trend in the concentration of sVEGFR-3 was observed in preeclamptic women (p = 0.0586), irrespective of HIV status. Across all groups, the concentration of sVEGFR-2 was significantly downregulated in HIV-positive PE (p = 0.0053) and the expression of sVEGFR-3 was significantly reduced in HIV-negative PE (p = 0.0393), compared to HIV-negative PE. Conclusion: This novel investigation reports a significant downregulation of serum sVEGFR-2 and a downward trend in the serum expression of sVEGFR-3 in preeclamptic compared to normotensive pregnancies. The hypoxic microenvironment of PE is associated with endothelial cell damage which greatly contributes to the decreased serum expression of sVEGFR-2 and sVEGFR-3. The use of antiretroviral therapy (ART) reconstitutes the immune response in HIV-positive preeclamptic women; hence, it significantly contributes to the risk of developing PE. Furthermore, the HIV-1 trans-activator of transcription protein mimics the behaviour of vascular endothelial growth factors (VEGF) due to their structural homology; however, this does not counterbalance the decline of VEGF in PE due to the administration of ART. In addition, the association of pregnancy with an upregulation of angiotensin converting enzyme 2 receptors increases the risk of pregnant women being infected with SARS-CoV- 2. Further investigations are essential to critically evaluate the influence of HIV infection and the epigenetic regulation of these soluble anti-angiogenic factors.