Folic acid supplementation on inflammation and homocysteine in type 2 diabetes mellitus: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The beneficial effects of folate have been observed under different conditions, but the available evidence on inflammation and reduction of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) is limited. The study aimed to explore the effects of folate on inflammation and homocysteine amongst individuals with T2DM. METHODS: PubMed, Scopus, and Cochrane Library were used to search for evidence. A random-effect model meta-analysis through Review Manager (version 5.4) and metaHun was performed. Results were reported as standardized mean differences (SMD) and 95% confidence intervals graphically using forest and funnel plots. RESULTS: Data from 9 trials with 426 patients living with T2DM were analyzed. Folic acid supplementation significantly revealed a large effect size on homocysteine levels compared to placebo, SMD = -1.53, 95%CI (-2.14,-0.93), p < 0.05. Additionally, we observed a medium marginal effect size on C-reactive protein (SMD = -0.68, 95%CI (-1.34, -0.01), p = 0.05). However, no significant effect on tumor necrosis factor-α (SMD = -0.86, 95%CI (-2.65, 0.93), p = 0.34), and interleukin-6 (SMD = -0.04, 95%CI (-1.08, 1.01), p = 0.95) was observed. CONCLUSION: Evidence analyzed in this study suggests that folic acid supplementation in T2DM reduces homocysteine and may mitigate CVDs. However, its effect on inflammation is inconclusive.

Association of carotid intima-media thickness and dyslipidaemia in patients with type 2 diabetes: a protocol for systematic review and meta-analysis.

INTRODUCTION: Patients with diabetes mellitus (DM) often present with comorbidities such as hypertension, dyslipidaemia, insulin resistance, obesity and hyperglycaemia, which increases their risk of cardiovascular diseases (CVDs)-related mortality. Carotid intima-media thickness (CIMT), a biomarker for subclinical atherosclerosis, has been associated with overall CVD, especially in type 2 DM (T2DM). Hence, this protocol for systematic review and meta-analysis aims to review existing literature on the association of CIMT and dyslipidaemia in patients with T2DM. METHODS AND ANALYSIS: The proposed systematic review and meta-analysis will be conducted according to an updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols guideline. A comprehensive search of peer-reviewed studies on Google Scholar, PubMed, Science Direct and Web of Sciences databases will be conducted up to 30 June 2023. A meta-analysis of data extracted from selected studies will be performed to explore the association between dyslipidaemia and CIMT in patients with diabetes. The effect estimates will be reported as standardised mean differences/Cohen's d and 95% CIs. A random effect model will be used in case of high heterogeneity whereas fixed-effect model will be used in the absence of heterogeneity. All statistical analysis will be performed using SPSS V.29.0 software. In cases of high heterogeneity, subgroup analysis will be performed based on study design, countries of publication and body mass index to identify potential sources of heterogeneity. Publication bias will be assessed graphically via funnel plots and statistically using Egger's regression test. Sensitivity analysis will also be performed to evaluate the stability of the overall effect size and the grading of recommendations assessment, development and evaluation will be used to grade the quality of analysed evidence. ETHICS AND DISSEMINATION: As the proposed study will use secondary published data, approval will not be sought from the ethics committee. PROSPERO REGISTRATION NUMBER: CRD42023451731.

Endothelial dysfunction, a predictor of cardiovascular disease in HIV patients on antiretroviral therapy: A systematic review and meta-analysis.

Aim Although antiretroviral therapy (ART) is available, the rate of new HIV infections is alarming. With this trend, it is anticipated that the use of ART will continue to rise, potentially resulting in associated vascular disorders. Therefore, we aimed to examine the impact of ART on endothelial function in people living with HIV (PLHIV), a predictor of cardiovascular diseases. METHOD: A comprehensive search for evidence was made on PubMed and Scopus on May 06, 2023, following the Preferred Reporting Items for Systematic Review and Meta-analysis. Cochrane and Newcastle-Ottawa quality assessment scales were used to evaluate quality, while the metaHun web tool and Review Manager version 5.4.1 were used for analysis. Subgroup, sensitivity, and publication bias were conducted for each outcome measure. RESULTS: We identified 37 studies, including a sample size of 3700 with 2265 individuals on ART. The analyzed evidence showed a large significant effect of ART on vascular cell adhesion molecule-1, with a standardized mean difference (SMD) of -1.23 (95 % CI: -1.72, -0.74; p = 0.0013). Similarly, a significant medium effect of ART was observed on intercellular cell adhesion molecule-1 in PLHIV, with an SMD of -1.28 (95 % CI: -2.00, -0.56; p = 0.0231) compared to the control group. Furthermore, ART exhibited a significant but small effect on flow-mediated dilation (FMD) with an SMD of -0.40 (95 % CI: -0.62, -0.19, p = 0.0159). CONCLUSION: Our findings show an improved endothelial function in PLHIV on ART, as demonstrated by reduced adhesion molecules; however, ART exhibited a small effect on FMD, thus suggesting PLHIV on ART may still be at risk of endothelial dysfunction and further cardiovascular diseases.

Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia.

BACKGROUND: Evidence from preclinical studies has found a correlation between the development of type 2 diabetes (T2D) and vitamin D deficiency. However, evidence from randomized controlled trials (RCTs) revealed inconclusive results on vitamin D supplementation. We explored the effect of vitamin D on inflammation and dyslipidemia in T2D. METHODS: We comprehensively searched for RCTs evaluating the effect of vitamin D in T2D on PubMed. Data were analyzed using Review Manager 5.3 and reports, such as standardized mean difference (SMD) and 95% confidence intervals (CI) at a 5% significant level using a random effect model. RESULTS: This study revealed a significant reduction in tumor necrosis factor-alpha (TNF-α) SMD = (-0.51, 95%CI (-0.93, -0.09); p = 0.02), high sensitivity C-reactive protein (hs-CRP) SMD = (-1.06, 95%CI (-1.67, -0.45); p < 0.05) in vitamin D compared to placebo. Additionally, interleukin-6 (IL-6) exhibited a marginal effect SMD = (-0.52, 95%CI (-1.05, 0.01), p = 0.05). Furthermore, a significant reduction in the level of triglycerides SMD = (-0.65, 95%CI (-1.11, -0.18), p < 0.05) was observed, concomitant to a significantly increased high-density lipoprotein (HDL) level SMD = (0.53, 95%CI (0.08, 0.98), p = 0.02). However, no statistically significant changes were observed in total cholesterols SMD = (-0.16, 95%CI (-0.57, 0.24), p = 0.43) and low-density lipoprotein (LDL) SMD = (-0.06, 95%CI (-0.37, 0.24), p = 0.67). CONCLUSIONS: These findings suggest that vitamin D supplementation may be beneficial in ameliorating inflammation and dyslipidemia in T2D patients.

Comprehensive Overview of the Effects of Amaranthus and Abelmoschus esculentus on Markers of Oxidative Stress in Diabetes Mellitus.

The use of medicinal plants in the management of diabetes mellitus (DM) is extensively reported. However, there is still very limited information on the role of these plants as markers of oxidative stress in DM. This current review evaluated the effect of Amaranthus spinosus, Amaranthus hybridus, and Abelmoschus esculentus on markers of oxidative stress in rodent models of DM. Current findings indicate that these plants have the potential to reduce prominent markers of oxidative stress, such as serum malondialdehyde and thiobarbituric acid-reactive substances, while increasing enzymes that act as antioxidants, such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase. This may reduce reactive oxygen species and further ameliorate oxidative stress in DM. Although the potential benefits of these plants are acknowledged in rodent models, there is still a lack of evidence showing their efficacy against oxidative stress in diabetic patients. Therefore, we recommend future clinical studies in DM populations, particularly in Africa, to evaluate the potential effects of these plants. Such studies would contribute to enhancing our understanding of the significance of incorporating these plants into dietary practices for the prevention and management of DM.

A Review on Inflammasomes and Immune Checkpoints in Pre-Eclampsia Complicated with Tuberculosis and Human Immune Deficiency Virus.

The current review evaluates how inflammasomes and immune checkpoints are regulated in pre-eclampsia (PE) associated with tuberculosis (TB) and Human Immune Deficiency Virus (HIV). Studies indicate that inflammasomes such as (NRLP3, NEK7, and AIM2) and immune checkpoints such as (CLT4, PD-1, TIM3, and LAG-3) are dysregulated in TB- and HIV-infected individuals, and also in pre-eclamptic pregnancies, which explains why pregnant women who are either infected with TB or HIV have an increased risk of developing PE. Evidence suggests that inhibition of inflammasomes and immune checkpoints may assist in the development of novel anti-inflammatory drugs for the prevention and management of PE in patients with or without TB and HIV infection.

The Impact of Punica granatum Linn and Its Derivatives on Oxidative Stress, Inflammation, and Endothelial Function in Diabetes Mellitus: Evidence from Preclinical and Clinical Studies.

Diabetes mellitus is recognized as the leading contributor to cardiovascular disease and associated mortality rates worldwide. Despite the use of pharmaceutical drugs to treat diabetes, its prevalence continues to rise alarmingly. Therefore, exploring remedies with a lower toxicity profile is crucial while remaining safe and effective in addressing this global public health crisis. Punica granatum Linn (pomegranate), known for its properties and safety profile, has been investigated in applied research and preclinical and clinical trials. However, conflicting reports still exist regarding its effects in diabetes. According to our knowledge, no systematic review has been conducted to critically analyze evidence from preclinical and clinical trials simultaneously, explicitly focusing on oxidative stress, inflammation, and endothelial function in diabetes. Therefore, in this systematic review, we searched for evidence on the impact of pomegranate in diabetes using databases such as PubMed, Scopus, and Google Scholar. Our inclusion criteria were limited to studies published in English. Of the 170 retrieved studies, 46 were deemed relevant and underwent critical analysis. The analyzed evidence suggests that pomegranate has the potential to alleviate oxidative stress, inflammation, and endothelial dysfunction in diabetes. Although a beneficial impact was noted in these markers, the endothelial function evidence still requires validation through further clinical trials with a powered sample size.

A Systematic Review and Meta-Analysis on the Impact of Statin Treatment in HIV Patients on Antiretroviral Therapy.

The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group of patients, ARTs are associated with risk of cardiovascular diseases (CVD). Moreover, virally suppressed patients still experience immune activation associated with HIV migration from reservoir sites. Statins are widely recommended as therapeutic agents to control ART-related CVD; however, their impacts on the cluster of differentiation (CD)4 count and viral load are inconsistent. To assess the effect of statins on markers of HIV infections, immune activation and cholesterol, we thoroughly reviewed evidence from randomised controlled trials. We found 20 relevant trials from three databases with 1802 people living with HIV (PLHIV) on statin-placebo treatment. Our evidence showed no significant effect on CD4 T-cell count standardised mean difference (SMD): (-0.59, 95% confidence intervals (CI): (-1.38, 0.19), p = 0.14) following statin intervention in PLHIV on ART. We also found no significant difference in baseline CD4 T-cell count (SD: (-0.01, 95%CI: (-0.25, 0.23), p = 0.95). Our findings revealed no significant association between statins and risk of viral rebound in PLHIV with undetectable viral load risk ratio (RR): (1.01, 95% CI: (0.98, 1.04), p = 0.65). Additionally, we found a significant increase in CD8+CD38+HLA-DR+ T-cells (SMD (1.10, 95% CI: (0.93, 1.28), p < 0.00001) and CD4+CD38+HLA-DR+ T-cells (SMD (0.92, 95% CI: (0.32, 1.52), p = 0.003). Finally, compared to placebo, statins significantly reduced total cholesterol (SMD: (-2.87, 95% CI: (-4.08, -1.65), p < 0.0001)). Our results suggest that the statin lipid-lowering effect in PLHIV on ART may elevate immune activation without influencing the viral load and CD4 count. However, due to the limited evidence synthesised in this meta-analysis, we recommend that future powered trials with sufficient sample sizes evaluate statins' effect on CD4 count and viral load, especially in virally suppressed patients.

Immunological Imbalances Associated with Epileptic Seizures in Type 2 Diabetes Mellitus.

PURPOSE OF THE REVIEW: Type 2 diabetes mellitus (T2DM) is a global health burden that leads to an increased morbidity and mortality rate arising from microvascular and macrovascular complications. Epilepsy leads to complications that cause psychological and physical distress to patients and carers. Although these conditions are characterized by inflammation, there seems to be a lack of studies that have evaluated inflammatory markers in the presence of both conditions (T2DM and epilepsy), especially in low-middle-income countries where T2DM is epidemic. Summary findings: In this review, we describe the role of immunity in the seizure generation of T2DM. Current evidence shows an increase in the levels of biomarkers such as interleukin (IL-1ß, IL-6, and IL-8), tumour necrosis factor-α (TNF-α), high mobility group box-1 (HMGB1), and toll-like receptors (TLRs) in epileptic seizures and T2DM. However, there is limited evidence to show a correlation between inflammatory markers in the central and peripheral levels of epilepsy. CONCLUSIONS: Understanding the pathophysiological mechanism behind epileptic seizures in T2DM through an investigation of immunological imbalances might improve diagnosis and further counter the risks of developing complications. This might also assist in delivering safe and effective therapies to T2DM patients affected, thus reducing morbidity and mortality by preventing or reducing associated complications. Moreover, this review also provides an overview approach on inflammatory cytokines that can be targeted when developing alternative therapies, in case these conditions coexist.

Corchorus olitorius extract exhibit anti-hyperglycemic and anti-inflammatory properties in rodent models of obesity and diabetes mellitus.

Obesity and type 2 diabetes (T2D) are chronic conditions with detrimental impacts on the overall health of individuals. Presently, the use of pharmacological agents in obesity and T2D offers limited benefits and pose side effects. This warrant studies on remedies that are less toxic and inexpensive while effective in ameliorating secondary complications in obesity and T2D. Plant-based remedies have been explored increasingly due to their remarkable properties and safety profile. We searched for pre-clinical evidence published from inception until 2023 on PubMed, Scopus, Google, and Semantic scholar on Corchorus olitorius (C. olitorius) in both obesity and T2D. Our focus was to understand the beneficial impact of this plant-based remedy on basic glycemic, lipid, inflammatory, and biomarkers of oxidative stress. The evidence gathered in this review suggests that C. olitorius treatment may significantly reduce blood glucose, body weight, total cholesterol, triglycerides, and low-density lipoprotein (LDL) in concomitant with increasing high-density lipoprotein-cholesterol (HDL-c) in rodent models of obesity and T2D. Interestingly, this effect was consistent with the reduction of malonaldehyde, superoxide dismutase and catalases, tumor necrosis factor-alpha, interleukins, and leptin. Some of the mechanisms by which C. olitorius reduces blood glucose levels is through stimulation of insulin secretion, increasing ß-cell proliferation, thus promoting insulin sensitivity; the process which is mediated by ascorbic acid present in this plant. C. olitorius anti-hyperlipidemia is attributable to the content of ferulic acid found in this plant, which inhibits 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors and thus results in reduced synthesis of cholesterol and increased hepatic LDL-c receptor expression, respectively. The present review provides extensive knowledge and further highlights the potential benefits of C. olitorius on basic metabolic parameters, lipid profile, inflammation, and oxidative stress in rodent models of obesity and T2D.

Interrelationships between migraine over the counter (OTC) painkillers and hypertensive disorders of pregnancy: A protocol for systematic review and meta-analysis.

BACKGROUND: Migraine during pregnancy is common and has been reported to affect up to 10% of pregnancies. Irrespective of the type of migraine, over the counter (OTC) painkillers are used as a migraine treatment plan. Growing evidence suggests that OTC painkillers have effects on the mother, the child and hypertensive disorders of pregnancy, including hypertension, eclampsia and pre-eclampsia, but inconsistent findings have been reported. The aim of this study is therefore to investigate the association between the use of migraine OTC painkillers and hypertensive disorders during pregnancy. METHODS: Databases such as Pubmed, Cochrane library, ScienceDirect and google scholar will be searched to identify eligible studies. Studies will be included if they are randomised controlled trials, cohort, and matched cohort, and cross-sectional studies of pregnant women with reported use of OTC painkillers to treat migraines at any stage of their pregnancy. The results will be reported based on the preferred reporting items for systematic reviews and meta-analysis 2009 statement, and article screening and selection process will also be demonstrated through a preferred reporting items for systematic reviews and meta-analysis for protocols flow diagram. The data will then be extracted by 1 reviewer and checked by another for accuracy. The quality and risk of bias of eligible studies will be performed by both reviewers using the Hoy tool and grading of recommendations assessment, development and evaluation tool. The data will be analysed using Review Manager 5.3 (RevMan 5.3) software. ETHICS AND DISSEMINATION: The review and meta-analysis will not require ethical approval and the findings will be published in peer-reviewed journals and presented at local and international conferences. Findings from this study will help to improve knowledge on the understanding of the effects OCT on hypertensive disorders of pregnancy. This study will also provide new information on the management of migraine during pregnancy. SYSTEMATIC REVIEW REGISTRATION: International prospective Register of Systematic Reviews (PROSERO) number: CRD42021232232.

Effect of antidepressants in pregnancy outcomes: A protocol for systematic review and meta-analysis.

BACKGROUND: Depression is much more common in women pre their pregnancies with antidepressants use less common which is caused by when many patients opt to discontinue with the use due to its side effects it causes. But whether depression is treated by antidepressants or not this has the same negative pregnancy outcomes on both the mother and the unborn and even born child from these mothers. METHODS: Information will be retrieved for this systematic review and meta-analysis study on antidepressants use pregnancy outcomes from PubMed and Google scholar search engines using search medical subjects headings on PubMed and the PICOS framework as the determinant of the research question. All returned articles searched will be stored to Zotero.org and the software RevMan will be used to analyze data. ETHICS AND DISSEMINATION: The review and meta-analysis will not require ethical approval and the findings will be published in peer-reviewed journals and presented at local and international conferences. In addition, findings from this study will assist in assessing health related risk outcomes of antidepressants during- and postpregnancy on both the fetal and mother either when used pre- and during-pregnancy. SYSTEMATIC REVIEW REGISTRATION: International prospective Register of Systematic Reviews (PROSERO) number: CRD42021232111.

Association of tuberculosis treatment with pregnancy complications: A protocol for systematic review and meta-analysis.

BACKGROUND: The increasing burden of tuberculosis (TB) remains a very serious concern around the world, and account for a decreased quantity and quality of life. However, there is a limited epidemiology of the association of TB treatment with pregnancy. We aim to assess the effects of TB treatment in pregnancy complications. METHODS: This will be a systematic review and meta-analysis of published studies on the association of TB treatment with pregnancy, retrieved from ScienceDirect, Web of Science, LILACS, Pubmed, Google scholar, Embase, Medline, ResearchGate, EBSCOhost and Cochrane library databases. The eligibility of the studies will be screened in accordance to the selection criteria by two independent reviewers. The quality and risk of bias of eligible studies will be performed by both reviewers using the Hoy tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool in accordance to the measured outcomes (Hypertension in pregnancy, Pre-eclampsia, Hypertensive disorders of pregnancy, Fetal growth restriction, Miscarriage and Recurrent spontaneous abortion). A data charting table will be used to extract background information and process the data items from each eligible study. The data will be analysed using Review Manager 5.3 (RevMan 5.3) software. Generic Inverse Variance method will be used for meta-analysis of both, individually and cluster randomized trials. ETHICS AND DISSEMINATION: The review and meta-analysis will not require ethical approval and the findings will be published in peer-reviewed journals and presented at local and international conferences. In addition, the study findings will be made accessible to the national committee of TB to formulate TB guidelines for their respective settings. SYSTEMATIC REVIEW REGISTRATION: International prospective Register of Systematic Reviews (PROSERO) number: CRD42021231872.

The Role of Oxidative Stress in Hypertensive Disorders of Pregnancy (Preeclampsia, Gestational Hypertension) and Metabolic Disorder of Pregnancy (Gestational Diabetes Mellitus).

Purpose of the Review.To highlight the role of oxidative stress in hypertensive disorders of pregnancy (HDP) and metabolic disorders of pregnancy (gestational diabetes mellitus). Recent Findings. In both preeclampsia (PE) and gestational hypertension (GH), oxidative stress leads to inadequate placental perfusion thus resulting in a hypoxic placenta, which generally leads to the activation of maternal systemic inflammatory response. In PE, this causes inflammation in the kidneys and leads to proteinuria. A proteinuria marker known as urinary 8-oxoGuo excretion is expressed in preeclampsia. In GDM, oxidative stress plays a role in the pathogenesis of the disease, as a result of over secretion of insulin during pregnancy. This uncontrolled secretion of insulin results in the production of lipid peroxidation factors that also mask the secretion of antioxidants. Therefore, ROS becomes abundant at cellular level and prevents the cells from transporting glucose to body tissues. Summary. There is a need for more research investigating the role of oxidative stress, especially in obstetrics-related conditions. More studies are required in order to understand the difference between the pathogenesis and pathophysiology of PE versus GH since investigations on the differences in genetic aspects of each condition are lacking. Furthermore, research to improve diagnostic procedures for GDM in pregnancy is needed.

The Role of HIV Infection in the Pathophysiology of Gestational Diabetes Mellitus and Hypertensive Disorders of Pregnancy.

Purpose of the Review: The main objective of this study is to investigate mechanisms associated with gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) in HIV infected pregnant women by looking how placental hormones such as (progesterone and prolactin) and basic haemostatic parameters are regulated in HIV infected pregnancies. Recent Findings: HIV/AIDS are a major global obstetric health burden that lead to increased rate of morbidity and mortality. HIV/AIDS has been associated with the pathophysiology of GDM and HDP. Increased risk of GDM due to highly active antiretroviral therapy (HAART) usage has been reported in HIV infected pregnancies, which causes insulin resistance in both pregnant and non-pregnant individuals. HAART is a medication used for lowering maternal antepartum viral load and pre-exposure and post-exposure prophylaxis of the infant. In pregnant women, HAART induces diabetogenic effect by causing dysregulation of placental hormones such as (progesterone and prolactin) and predispose HIV infected women to GDM. In addition to HIV/AIDS and GDM, Studies have indicated that HIV infection causes haemostatic abnormalities such as hematological disorder, deregulated haematopoiesis process and the coagulation process which results in HDP. Summary: This study will help on improving therapeutic management and understanding of the pathophysiology of GDM and HDP in the absence as well as in the presence of HIV infection by reviewing studies reporting on these mechanism.

The Association of Tuberculosis Mono-infection and Tuberculosis-Human Immunodeficiency Virus (TB-HIV) Co-infection in the Pathogenesis of Hypertensive Disorders of Pregnancy.

PURPOSE OF REVIEW: This review highlights the impact of TB mono-infection and TB-HIV co-infection on the pathogenesis of adverse maternal outcomes such as hypertensive disorders of pregnancy (HDP) and adverse fetal outcomes such as recurrent spontaneous abortion (RSA), fetal growth restriction (FGR), and low birth weight. RECENT FINDINGS: Research has shown that HDP, such as severe pre-eclampsia (PE) and eclampsia, as well as adverse fetal outcomes such as recurrent spontaneous abortion, fetal growth restriction, and low birth weight, are higher in women diagnosed with TB mono-infection and even higher in TB-HIV co-infection compared to those without TB. This is speculated to occur due to exaggerated activation of both angiogenic factors such as vascular endothelial growth factor (VEGF), nitric oxide (NO), angiotensin 2, (Ang 2), intracellular adhesion molecules (ICAMs), and inflammatory cytokines such as interleukin 2 (IL-2), (IL-17), and interferon-gamma (INF-γ). There is a lack of information with regard to the pathogenesis of adverse maternal and fetal outcomes upon TB mono-infection and TB-HIV co-infection; therefore, further investigations on the impact of TB mono-infection and TB-HIV co-infection on adverse maternal and fetal outcomes are urgently needed. This will assist in improving diagnostic procedures in pregnant women affected with TB as wells as TB-HIV co-infection.

Is pregnancy a risk factor of COVID-19?

This review evaluates whether pregnancy is a risk factor for COVID-19 by looking at the expression of immune markers such as immune cells and cytokines in order to have a better understanding on the pathophysiology of the disease, thus reducing maternal deaths. Pregnant women are more at risk of contracting COVID-19 due to their weakened immune system. Studies demonstrate that COVID-19 is an immune condition which is marked by reduced lymphocytes and elevated selected proinflammatory cytokines. Similar immune expression has been demonstrated in pregnancy by several studies. In addition, the placenta has been shown to possess ACE2 receptors on the villous cytotrophoblast and the syncytiotrophoblast and findings suggest that the coronavirus enters the host cells via these ACE2 receptors. The immune response in pregnancy increases the risk of contracting COVID-19. Both normal pregnancy and COVID-19 are marked by decreased lymphocytes, NKG2A inhibitory receptors, and increased ACE2, IL-8, IL-10, and IP-10 it therefore safer to conclude that pregnancy is a risk factor for COVID-19 development. Furthermore, the presence of the ACE2 receptors in the placenta may increase the risk of mother to baby transmission of the virus. Therefore, more studies investigating the link between pregnancy and COVID-19 are needed.

The Role of Highly Active Antiretroviral Therapy (HAART) on Interleukin 17A (IL-17A) in Normotensive and Preeclamptic Black South African Women.

Introduction: Interleukin 17A has been implicated in the pathophysiology of both human immune deficiency virus and preeclampsia. This study evaluated serum levels of IL-17A based on pregnancy type, gestational age, HIV status, and duration of HAART. Material and Methods. A sample size of 250 was analysed: normotensives (n = 150; N) and preeclamptics (n = 100; PE). Normotensives were further stratified into HIV negative (n = 90), HAART-acute (n = 30), and HAART-chronic (n = 30). The PE group was divided into early onset (n = 50; EOPE) and late onset (n = 50; LOPE). The EOPE and LOPE groups were subdivided into HIV negative (n = 30), HAART-acute (n = 10), and HAART-chronic (n = 10). Analysis of IL-17A was performed using a multiple Bio-Plex immunoassay method. Results: Pregnancy type: the levels of IL-17A were increased in PE compared to N (P = 0.0014). Gestational age: the levels of IL-17A were increased in EOPE compared to N group (P = 0.0113). A significant increase in the levels of IL-17A in LOPE compared to N was observed (P = 0.0063). HIV status: the levels of IL-17A were increased in PE compared to N (P = 0.0114) and in EOPE compared to N groups (P = 0.0071). HAART duration: the concentration of IL-17A was increased in HAART-chronic PE compared to N groups (P = 0.0062). There was also an increase in the levels of IL-17A in EOPE compared to N (P = 0.0029). Conclusion: The study demonstrates that IL-17A is involved in the pathophysiology of PE and that in the presence of HIV infection, chronic HAART administration predisposes women to the development of EOPE.

HLA-G Polymorphisms Associated with HIV Infection and Preeclampsia in South Africans of African Ancestry.

OBJECTIVES: HLA-G, part of the major histocompatibility complex (MHC), is associated with the risk of developing preeclampsia (PE). In this study, we determined the contribution of specific HLA-G polymorphisms on the risk of developing preeclampsia in HIV-infected and uninfected South Africans of African ancestry. METHODS: One hundred and ninety-three women of African ancestry were enrolled (74 HIV-uninfected normotensive, 60 HIV-infected normotensive, 34 HIV-uninfected, and 25 HIV-infected preeclamptics). Sanger sequencing of the untranslated region was performed to genotype six SNPs, i.e., 14 bp Ins/Del of rs66554220, rs1710, rs1063320, rs1610696, rs9380142, and rs1707). RESULTS: For rs66554220, we have the following results: (a) based on pregnancy type-the Ins/Ins and Del/Ins genotype frequency was higher in preeclampsia (PE) compared to normotensive pregnancies (Ins/Ins vs. Del/Ins, P = 0.02∗: OR (95%CI) = 13.44 (0.7222-249.9); Del/Del vs. Del/Ins, P = 0.03∗: OR (95%CI) = 2.95 (1.10-7.920)); (b) based on HIV status-the Ins/Ins showed both genotypic and allelic association with HIV infection. HIV-infected PE has higher Ins/Ins genotypic and allelic frequencies compared to HIV-uninfected PE (Ins/Ins vs. Del/Ins, P = 0.005∗∗: OR (95%CI) = 21.32 (1.71-4.17); Ins, P = 0.005∗∗; OR (95%IC) = 21.32 (1.71-4.17)). For rs1707, we have the following results: (a) based on pregnancy type-there were CT genotypic frequencies in PE, more especially LOPE compared to normotensive pregnancies (TT vs. CT, P = 0.0092∗∗: OR (95%CI) = 5.(1.39 - 25.64)), and no allelic association was noted; (b) based on HIV status-CT was higher in HIV-infected LOPE compared to uninfected LOPE (TT vs. TC, P = 0.0006∗∗∗: OR (95%CI) = 40.00 (2.89 - 555.1)). For rs1710 and rs1063320, no significant differences in the genotype and allele frequencies were noted based on pregnancy type and HIV status. For rs9380142, we have the following results: (a) based on pregnancy type-no significant differences were noted between normotensive compared to PE pregnancies; (b) based on HIV status-AA genotypes occurred more in the HIV-infected PE group (AA vs. GG, P = 0.02∗: OR (95%CI) = 13.97 (0.73 - 269.4)), while A allelic frequency occurred more in HIV-infected PE, especially LOPE compared to uninfected groups (A vs. G, P = 0.0003∗∗∗: OR (95%CI) = 10.72 (2.380 - 48.32); P = 0.02∗: OR (95%CI) = 9.00 (1.07 - 75.74)). For rs1610696, we have the following results: (a) based on pregnancy type-genotypic and allelic frequencies of CC were higher in PE compared to normotensive pregnancies (CC vs. GG, P = 0.0003∗∗∗: OR (95%CI) = 31.87 (1.861 - 545.9); C, P = 0.0001∗∗∗: OR (95%IC) = 21.91 (2.84 - 169.0)); (b) based on HIV status-GG frequencies were higher in the HIV-infected PE more especially LOPE groups (GG vs. GC, P = 0.02∗: OR (95%CI) = 16.87 (0.81 - 352.1); GG vs. CC, P = 0.0001∗∗∗: OR (95%CI) = 159.5 (13.10 - 1942)). CONCLUSION: Selected HLA-G 14 bp polymorphisms (Ins/Ins) and genotypic and allelic differences in rs9380142, rs1610696, and rs1707 are associated with the pathogenesis of preeclampsia in HIV-infected South African women of African ancestry. More genetic studies evaluating the association between preeclampsia and HIV infection are needed to improve diagnosis and antenatal care.

Dopamine in the Pathophysiology of Preeclampsia and Gestational Hypertension: Monoamine Oxidase (MAO) and Catechol-O-methyl Transferase (COMT) as Possible Mechanisms.

PURPOSE OF THE REVIEW: Hypertension in pregnancy is the global health burden. Amongst the hypertensive disorders of pregnancy, preeclampsia and gestational hypertension are the world's leading disorders that lead to both maternal and fetal morbidity and mortality. RECENT FINDINGS: Dopamine inactive metabolites, namely, monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT), have been reported to be associated with hypertensive disorders of pregnancy such preeclampsia and gestational hypertension. SUMMARY: This review discusses the involvement of MAO and COMT in the pathophysiology of both conditions in order to have a better understanding on the pathogenesis of both conditions, suggesting promising therapeutic interventions and subsequently reducing maternal and fetal morbidity and mortality.