Covid-19 pandemic: Perspectives on management.

The pandemic COVID-19 presents a major challenge to identify effective drugs for treatment. Clinicians need evidence based on randomized trials regarding effective medical treatments for this infection. Currently no effective therapies exist for the progression of the mild forms to severe disease. Knowledge however is rapidly expanding. Remdesivir, an anti- retroviral agent has in vitro activity against this virus and has shown to decrease the duration of ICU care in patients with severe disease, while low dose dexamethasone also showed a decrease in the duration of stay in cases of severe disease requiring assisted ventilation. At the time of writing this article, two mRNA-based vaccines have shown an approximate 95 % efficacy in preventing infection in large clinical trials. At least one of these drugs has regulatory permission for vaccination in high-income countries. Low and middle-income countries may have difficulties in initiating vaccine programs on large scales because of availability, costs, refrigeration and dissemination. Adequately powered randomized trials are required for drugs with in vitro activity against the virus. Supportive care should be provided for stable, hypoxia and pneumonia free patients on imaging. Vaccines are of obvious benefit and given the preliminary evidence of the efficacy of over 95 %, Low and middle-income countries must develop links with the WHO COVAX program to ensure global distribution of vaccines.

The Renin-Angiotensin System, Hypertension, and SARS-CoV-2 Infection: a Review.

PURPOSE OF REVIEW: This review focuses on the associations between the renin-angiotensin system, hypertension, and severe acute respiratory syndrome (SARS-COV-2) infection. A brief prelude on the current state of affairs with COVID-19 is given. In addition to an overview of ACE2, Ang II, and Ang (1-7), this review presents a brief statement on hypertension, including the function of enzymes involved in the control of hypertension, cardiovascular disease, diabetes mellitus, and other malignancies. RECENT FINDINGS: There is currently no data in support of the concerns raised with the use of ACEIs/ARBs. Many researchers have voiced concerns that the use of ACEIs and ARBs may increase tissue ACE2 levels. These researchers therefore recommend that individuals on ACEIs/ARB's medications withhold such antihypertensive drugs, unless advised by their physicians to do so. SARS-CoV-2 uses ACE2 receptors as the port of entry to human hosts. ACE2 and ACE are different enzymes and ACE inhibitors do not inhibit ACE2. Therefore, the use of ARB's or ACEIs should not be discontinued if an individual is infected by SARS-CoV-2. Further studies are required to investigate the effect of ACEIs and ARBs on ACE2 expression and COVID-19.

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 STATEMENTWhat 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.

The Role of the Renin-Angiotensin-Aldosterone System in Preeclampsia: a Review.

PURPOSE OF REVIEW: Preeclampsia (PE) is a complex human pregnancy-specific condition and is clinically characterized by new onset hypertension and proteinuria in the second half of pregnancy. The precise etiology of PE is unknown, but much of the pathophysiology has been elucidated, and it is accepted that the disorder is multifactorial in nature. Historically, because of the presence of proteinuria, the role of the renin-angiotensin-aldosterone system (RAAS) has been considered in the etiology of PE. However, the results of studies (including maternal circulatory angiotensin II, urinary angiotensinogen, plasma renin and prorenin, AT1 receptor antibodies, and gene polymorphisms) on the role of the RAAS in the etiology of PE have proved controversial. The purpose of this narrative review was to evaluate the contemporary literature on the RAAS and its role in the pathophysiology of pregnancy. RECENT FINDINGS: The current review shows that although the RAAS has a role in the development of normal pregnancy, it does not have a significant role in the pathophysiology of PE except for the AT1-AA components. Despite many researchers having measured increases in s[P}RR and [P]RR, this may be independent of the RAAS. Our view is in keeping with contemporary thinking that the placenta rather than the RAAS plays a central role in elaborating pro-inflammatory factors (antiangiogenic and angiogenic) into the maternal circulation resulting in widespread endothelial dysfunction in all organ systems including the renal system.

Angiogenesis, Lymphangiogenesis, and the Immune Response in South African Preeclamptic Women Receiving HAART.

Purpose of the review: This review highlights the role of angiogenesis, lymphangiogenesis, and immune markers in human immunodeficiency virus (HIV)-associated preeclamptic (PE) pregnancies in an attempt to unravel the mysteries underlying the duality of both conditions in South Africa. Recent findings: Studies demonstrate that HIV-infected pregnant women develop PE at a lower frequency than uninfected women. In contrast, women receiving highly active anti-retroviral therapy (HAART) are more inclined to develop PE, stemming from an imbalance of angiogenesis, lymphangiogenesis, and immune response. Summary: In view of the paradoxical effect of HIV infection on PE development, this study examines angiogenesis, lymphangiogenesis, and immune markers in the highly HIV endemic area of KwaZulu-Natal. We believe that HAART re-constitutes the immune response in PE, thereby predisposing women to PE development. This susceptibility is due to an imbalance in the angiogenic/lymphangiogenic/immune response as compared to normotensive pregnant women. Further large-scale studies are urgently required to investigate the effect of the duration of HAART on PE development.

Vitamin B6 deficiency alters tissue iron concentrations in the Wistar rat.

PURPOSE: We investigated the effect of a vitamin B6 deficiency and pair-feeding on tissue trace element status. METHOD: Tissue zinc, copper and iron concentrations were measured in 3 groups of young, male Wistar rats receiving a diet of 3.5mg/kg (control group), 0mg/kg (deficient group) and a pair-fed group over 8 weeks. The pair-fed group received the same diet consumed by the control. Tissue trace element analysis was performed using atomic absorption spectrophotometry and plasma vitamin B6 status was determined using HPLC. RESULTS: Deficiency resulted in elevation in liver iron concentration and reduction in muscle iron concentration. Muscle copper concentrations were reduced in the pair-fed and deficient groups vs. the control group. Tissue zinc concentrations remained unaffected by the deficiency. Kidney iron and heart copper levels were elevated in the pair-fed group. CONCLUSIONS: The liver and muscle iron changes were due to the deficiency and not to reduced calorie intake and the latter may be due to impaired heme synthesis. The differences in copper between the groups were due to reduced food intake. Zinc seems to form a fixed pool in these animals. A dietary deficiency of vitamin B6 impacts on the trace element status of certain tissues in key metabolic tissues and hence needs to be factored into the amelioration of the condition.

Evaluation of the behaviour of a thermal diffusion sensor in a high field strength magnetic resonance system: an experimental study.

Patients with acute brain pathology requiring ferromagnetic bio-medical implants for on-going invasive monitoring are largely excluded from the benefits of MRI scanning. We evaluated the behaviour of a thermal diffusion cortical blood flow (TD-CBF) sensor both in vitro (phantom gelatin model) and in vivo environments in a high field strength MRI system. Two baboons underwent cranial subdural implantation of 2 TD-CBF sensors/hemisphere and a single left parietal sensor was implanted subcortically to determine any deleterious effects. Using standard MRI sequences, artefact size, thermal effects, current generation, movement and reliability of recordings were assessed during scanning. The deflection forces were negligible, no observable thermal effects were demonstrated, while wide fluctuations in cerebral blood flow recordings were recorded. Mean image artefact size for implanted sensors was 6 times larger than in vitro. Patients with an implanted TD-CBF sensor may be safely imaged provided the device is disconnected. The MRI images obtained are of an acceptable quality.