The effect of vitamin B-6 deficiency on the levels of tissue copper, iron and zinc in the rat.

Thesis (M.Sc.)-University of Durban-Westville, 1989.No abstract available

METABOLIC EFFECTS OF TULBAGHIA VIOLACEA HARV. IN A DIABETIC MODEL.

Background: Diabetes mellitus (DM) is a cluster of metabolic diseases with chronic hyperglycemia as a defining feature, associated with long-term organ damage and dysfunction. In this study we examined the effect of Tulbaghia violacea rhizome methanolic extract on blood glucose and lipids in normal and streptozotocin-induced diabetic rats. Materials and Methods: Male Wistar rats (250-300g) were injected intraperitoneally (i.p.) with streptozotocin (60mg/kg body weight) to induce diabetes; or provided with distilled water for the control (CON) (3 ml/kg/b.w.) animals and treatment with TVL (60mg/kg.b.w). The rats were divided into 5 groups of 6 animals per group as follows: Non-diabetic control (NDC)-received distilled water (3ml/kg.b.w), Non-diabetic TVL (ND+TVL)-received TVL (60mh/kg b.w), Diabetic control (DC)-received distilled water (3ml/kg.b.w), Diabetic experimental (D+TVL)-received TVL (60mg/kg.b.w), Diabetic experimental (D+M)-received Metformin (250 mg/kg.b.w). All doses were administered daily via oral gavage. Results: TVL-treated animals showed reduced blood glucose, increased plasma insulin, reduced plasma TG, TC, VLDL and increased HDL. Furthermore we found decreased thiobarbituric acid reactive substances (TBARS) and increased superoxide dismutase (SOD) activity and nitric oxide significantly. Regarding renal parameters we found increased blood urea nitrogen (BUN), and improved renal morphology in TVL-treated animals. Conclusion: Tulbaghia violacea has a hypoglycaemic effect which could due to its effects on multiple pathways of the hyperglycemic process. Further work is needed to identify the mechanism of its antidiabetic effect

Circulating fetal and total cell-free DNA, and sHLA-G in black South African women with gestational hypertension and pre-eclampsia

Objective: Quantification of circulating fetal and total cell-free DNA (cfDNA) and soluble human leucocyte antigen (HLAG) in gestational hypertension and pre-eclampsia. Methods: Serum cfDNA were quantified in controls, pre-eclamptics, and gestational hypertensive patients using real-time qPCR. Soluble HLAG was measured by enzyme-linked immune-sorbent assay. Results: Serum fetal and total cfDNA levels were higher in pre-eclampsia compared with the controls and gestational hypertensives (p < 0.001), more so in severe compared with mild-to-moderate pre-eclampsia (p < 0.05). Soluble HLAG levels were lower in pre-eclamptics than controls and gestational hypertension (p < 0.05). Conclusion: Circulating fetal and total cfDNA were increased, while soluble HLAG was decreased in pre-eclampsia

An observational study of pro- and anti-angiogenic factors in hypertensive disorders of pregnancy in women of African ancestry

Hypertensive disorders in pregnancy (HDPs) are the leading cause of maternal and perinatal deaths worldwide. Despite the widely reported multisystemic pathophysiology of pre-eclampsia and other HDPs, it is unknown whether these disorders represent a continuum or separate entities making clinical diagnosis a challenge. This study aimed to investigate angiogenic, metabolic and immunoregulatory specific profiles of hypertensive and gestationally matched normotensive pregnancies. A total of 200 pregnancies from a regional hospital in South Africa, via convenience sampling, were quantitatively analysed for circulating sFlt-1; PlGF; VEGF; sENG; PAPP-A; PP13; ADAMTS 12; TGF-β1 in maternal serum samples using ELISA technique. Serum protein markers TGF-β1, sENG and PAPP-A were significantly increased (p < .05) in early-onset pre-eclampsia vs. NG1 groups. sFlt-1 was significantly higher in late-onset pre-eclampsia vs NG2 groups. The GH group showed a significant increase in TGF-β1 and PAPP-A vs. NG1 counterpart. ADAMTS12 and sENG were significantly lower in gestational hypertension vs. early-onset pre-eclampsia. No significant differences were seen in PlGF, VEGF and PP13 levels across the groups. These changes show the HDP spectrum has distinct characteristics on the angiogenic profile. Based on these results, further validation of diagnostic and prognostic biomarkers of pre-eclampsia and gestational hypertension is warranted.Impact statement What is already known on this subject? Hypertensive pregnancy disorders are a public health problem with adverse effects on both mother and neonate. The elusive pathogenesis of this syndrome combined with the late prevalence of symptoms leaves clinicians with a myriad of theories and indefinite treatments. The investigation into conventional anti-/angiogenic factors has been extensively studied in pre-eclampsia patients only. The overlapping clinical presentation of pre-eclampsia and gestational hypertension further complicates the diagnosis of disorders. What do the results of this study add? The investigation of novel angiogenic, metabolic and inflammatory markers will firstly contribute to generating a database for researchers both nationally and internationally. This combinatory triad of markers will assist in elucidating and differentiating between early- and late-onset preeclampsia versus gestational hypertension. The results of our cohort study suggest possible early diagnostic markers for pre-eclampsia and gestational hypertension. What are the implications of these findings for clinical practice and/or further research? Research in this area will contribute to an improvement in early disease management which will ultimately lead to a reduction in health care costs and mortality rate locally and globally. It will also enforce diagnostic and prognostic markers for hypertensive pregnancy diseases and warrant further investigation into the proteins primarily involved in the trophoblastic invasion. This will then clarify whether these two closely related hypertensive disorders represent a continuum or two separate entities

Differential expression of miRNAs are associated with the insulin signaling pathway in preeclampsia and gestational hypertension

Objectives: The objective of this study was to determine microRNAs (miRNAs) expression levels in placental tissue and serum samples from preeclampsia (PE) and gestational hypertensive (GH) patients. Study design: Using a targeted qPCR method, the selected miRNAs putatively involved in the PE and GH were examined from normotensive (n = 32), PE (n = 32) and GH (n = 28) in South African women. Western blot analysis of protein expressions of AKT and PI3K was performed in the placental tissue of all three groups. Results: qPCR results of serum miR-222 expression levels showed a significant decrease in PE compared to GH and normotensive groups. miR-29a expression levels were significantly increased in PE and GH groups compared to normotensives. Serum expression levels of miR-181a in GH showed a significant increase compared to the PE and normotensive groups. Placental tissue expression levels of miR-181a were significantly increased in PE and GH groups compared to normotensives. Western blot results of placental tissue showed a decrease in the expression levels of AKT-serine and threonine in the PE groups compared to the normotensives and a significantly higher expression in the GH groups compared to normotensives. Phosphatidyl-inositol-3 kinase (PI3K) expression levels were significantly decreased in PE and GH groups compared to normotensives. Conclusion: The present study, interestingly, demonstrates the differential expression of circulating miRNA in GH and a correlation between the expression levels of miRNAs with AKT/PI3K in the insulin signaling pathway, reinforcing the presence of metabolic dysregulation in PE and GH

Serum levels of vasoactive factors in HIV-infected pre-eclamptic women on HAART

In South Africa, pre-eclampsia (PE) and human immunodeficiency virus (HIV) infection are major causes of pregnancy-related deaths. This study aimed to measure serum levels of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PlGF) in HIV-infected highly active antiretroviral therapy (HAART)-treated and HIV-uninfected PE and normotensive women to ascertain if HIV/HAART alters their concentrations. Mean sFlt-1 levels were significantly up-regulated in the PE (HIV-uninfected 4.39 ± 1.29; HIV-infected 5.10 ± 1.10 ng/ml) compared to normotensive women (HIV-uninfected 2.59 ± 0.83; HIV-infected 2.20 ± 0.85 ng/ml). Mean PlGF levels were significantly lower in HIV-uninfected PE vs. HIV-infected normotensive women (29.69 ± 4.47 pg/ml vs. 32.86 ± 6.46 pg/ml; p = .002). In conclusion, PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels. Infection with HIV may have further increased the sFlt-1 levels.IMPACT STATEMENT What is already known on this subject? In PE, the numerous identified local and circulating bioactive factors differed in concentrations when compared to normal pregnancy. What do the results of this study add? PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels as well as increased levels of sFlt-1. What are the implications of these findings for clinical practice and/or further research? Understanding the link between PE, HIV and HAART during pregnancy will improve prognosis, management and treatment strategies for women clinically

Circulating exosomes in sepsis: A potential role as diagnostic biomarkers, therapeutic and drug delivery carriers

Sepsis and sepsis-related organ dysfunction have been identified as significant global life-threatening health threats, with a high mortality rate despite ongoing research in the area. Timely diagnosis is essential such that treatment could be initiated as early as possible to ensure the best outcome, since delayed intervention is associated with a higher mortality. Patient stratification and disease monitoring, present significant challenges in sepsis treatment and management strategies, largely due to the heterogenicity of sepsis signs and symptoms. Hence a focus on potential biomarkers to overcome these challenges is needed. Recently, extracellular vesicles (EVs), mainly the exosome subtype, have been investigated regarding their potential role in sepsis diagnostics, therapeutics and as drug delivery vehicles. Herein, we present an up-to-date review covering the role of circulating exosomes in the diagnosis and monitoring of the progression of sepsis and in therapeutics and drug delivery for sepsis. To provide context, sepsis pathophysiology and the role of circulating exosomes in sepsis have been highlighted. Future prospects, current challenges and recommendations regarding the role of exosomes in sepsis are also identified