Masters Degrees (Optics and Imaging)

Permanent URI for this collectionhttps://hdl.handle.net/10413/7053

Browse

Now showing 1 - 5 of 5

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 function of Adipsin and C9 protein in the complement system in HIV-associated preeclampsia.
(2020) David, Mikyle.; Naicker, Thajasvarie.; Moodley, Jagidesa.
Background Hypertensive disorders of pregnancy (HDP) and non-pregnancy related diseases (HIV, TB) are the most common causes of maternal mortality in South Africa (SA). Preeclampsia (PE), a complex medical disorder, accounts for the majority of maternal deaths emanating from HDP. In SA, the prevalence of HIV infection in pregnancy is high. The complement system, a part of our innate response, may be altered in the synergy of HIV infection and PE development. Complement activation at the maternal-interface may exacerbate inflammation, tissue injury, apoptosis as well as vascular leakage, in the complicated state of PE. The complement proteins, adipsin and C9, activates the body’s natural defence against HIV infection. C9 functions as a pore-forming component of the membrane attack complex. Moreover, the high rollout in SA of antiretroviral therapy may affect the immune response in HIV infected women. This study investigates the concentration of the complement proteins, Adipsin and C9 in the duality of HIV-associated PE. Method Samples of 38 normotensive and 38 preeclamptic patients, stratified further by HIV status were collected from a regional hospital. Thereafter, analysis of analytes via the Bio-plex Multiplex immunoassay occurred. Results Maternal weight did not differ (p = 0.1196) across the study groups. The concentration of adipsin was statistically different between the PE vs normotensive pregnant groups, irrespective of HIV status (p = 0.0439). There was no significant difference in adipsin concentration between HIV-negative vs HIV-positive groups, irrespective of pregnancy type (p = 0.6290). Additionally, there was a significant difference in adipsin concentration between HIV negative normotensive vs HIV negative preeclampsia (p < 0.05), as well as a difference between HIV negative preeclampsia vs HIV positive preeclampsia (p < 0.05). C9 protein expression was not statistically different between the normotensive and PE groups, regardless of HIV status (p =0.5365). No statistical significance in C9 expression was found between HIV positive vs HIV negative groups, regardless of pregnancy type (p = 0.3166). Similarly, no statistical significance was noted across all study groups (p= 0.0774). Conclusion This study demonstrates a significant up-regulation of adipsin in PE compared to normotensive pregnancies; this finding correlates with the exaggerated inflammatory milieu of PE. Complement C9 protein was similar between pregnancy types. This similarity may emanate from properdin dysregulation or a genetic polymorphism. The concentration of adipsin and C9 proteins were not affected by HIV status due to the immune reconstitution effect of antiretroviral therapy. Furthermore, the up-regulation of adipsin in placental sites and urinary levels of PE in previous studies, in tandem with our findings, indicate the possibility of adipsin as a predictor value for PE 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.
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.

Browse

Browsing Masters Degrees (Optics and Imaging) by Author "Moodley, Jagidesa."