Research Articles (Clinical Pharmacology)

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The 12-month period prevalence and cardiac manifestations of HIV in patients with acute coronary syndrome at a tertiary hospital in Cape Town, South Africa : a retrospective cross-sectional study
(BMC (part of Springer Nature), 2021) Pennefather, Camilla; Esterhuizen, Tonya; Doubell, Anton; Decloedt, Eric H.
Background: HIV-positive patients are increasingly being affected by non-communicable diseases such as coronary artery disease (CAD). Data from high-income countries (HICs) indicate that HIV-positive patients have different riskfactor profiles for acute coronary syndrome (ACS) as well as different cardiac manifestations of this syndrome compared to HIV-negative patients. There is limited data from Sub-Saharan Africa (SSA), and particularly from South Africa with the biggest HIV epidemic in the world. The objective of this study was to determine the 12-month period prevalence of HIV in patients with ACS and to compare the risk-factor profile, ACS presentation and management between HIV-positive and HIV-negative adults. Methods: We included all patients hospitalised with ACS from 01 January to 31 December 2018 in a tertiary hospital, Tygerberg Hospital, in Cape Town, South Africa. The HIV-status of all patients was determined using routine clinical records. We performed multiple conditional logistic regression on HIV-positive and HIV-negative patients (1:3 ratio) to compare the risk factor profile, ACS presentation and management between the groups. Results: Among 889 patients, 30 (3.4%) were HIV-positive (95% confidence interval (CI): 2.3–4.8). HIV-positive patients were younger, more frequently men, and had a lower prevalence of medical comorbidities and a family history of CAD. They were more likely to present with ST-elevation myocardial infarction (STEMI) [odd’s ratio (OR) (95% CI): 3.12 (1.2–8.4)], and have single-vessel disease [OR (95% CI): 3.03 (1.2–8.0)]. Angiographic and echocardiographic data, as well as management, did not differ between the groups. Among HIV-positive patients, 17 (65%) were virally suppressed (HIV viral load < 200 copies/mL) with a median CD4+ count of 271 cells/mm3. The majority (20, 67%) of HIV-positive patients were receiving antiretroviral therapy at the time of the ACS. Conclusions: We found an HIV-prevalence of 3.4% (95% CI 2.3–4.8) in adults with ACS in a high endemic HIV region. HIV-positive patients were younger and more likely to present with STEMIs and single-vessel disease, but had fewer CAD risk factors, suggesting additional mechanisms for the development of ACS.
A 3-year survey of acute poisoning exposures in infants reported in telephone calls made to the Tygerberg Poison Information Centre, South Africa
(Health & Medical Publishing Group, 2016-03) Marks, Carine J.; Van Hoving, D. J.
ENGLISH ABSTRACT: Background. Infants undergo rapid development changes and are particularly vulnerable to toxic chemicals. Identifying and evaluating the toxic risks that exist in this age group could be very valuable when making recommendations on how to prevent specific types of poisoning. Objectives. This study analysed the toxic substances responsible for acute poisoning exposures in infants (<1 year of age) as well as the severity of the exposures. Methods. A retrospective analysis of the Tygerberg Poison Information Centre (TPIC) database was conducted over a 3-year period (1 January 2011 to 31 December 2013). Descriptive statistics are provided for the entire study population as well as for the neonatal subgroup (<30 days old). Results. The TPIC handled 17 434 consultations during the 3-year study period. Infants were involved in 1 101 cases (6.3%), of which 46 cases (4.2%) were neonates. Most enquiries about infants were associated with non-drug chemicals (n=824, 74.8%). Pharmaceuticals were involved in 185 cases (16.8%) followed by biological exposures (e.g. snake and spider bites, scorpion stings, plant and mushroom poisonings) (n=109, 9.9%). Most infants (n=987, 89.6%) presented with no or only minor symptoms. In neonates, 17 (37.0%) presented with moderate to severe toxicity. Six of these (35.3%) were poisoned by complementary and alternative medicines. Conclusion. Most poisoning exposures in infants are not serious and can be safely managed at home after contacting a poison centre. Identification and documentation of poisoning in this special population is of great importance.
Aberrant apoptotic response of colorectal cancer cells to novel nucleoside analogues
(Public Library of Science, 2015) Harmse, Leonie; Dahan-Farkas, Nurit; Panayides, Jenny-Lee; Van Otterlo, Willem; Penny, Clement
Despite the increased understanding of colorectal cancer and the introduction of targeted drug therapy, the metastatic phase of the disease remains refractory to treatment. Since the deregulation of normal apoptosis contributes to the pathogenesis of colorectal cancer, novel nucleoside analogues were synthesized here and evaluated for their ability to induce apoptosis and cause cell death in two colorectal adeno-carcinoma cell lines, Caco-2 and HT-29. Three novel nucleoside analogues assessed here showed cytotoxic activity, as measured by the MTT assay against both cell lines: the IC50 values ranged between 3 and 37 μM, with Caco-2 cells being more sensitive than HT-29 cells. Compared to camptothecin, the positive control, the nucleoside analogues were significantly less toxic to normal unstimulated leukocytes (p>0.05). Moreover, the nucleosides were able to induce apoptosis as measured by an increase in caspase 8 and caspase 3 activity above that of the control. This was additionally supported by data derived from Annexin V-FITC assays. Despite marginal changes to the mitochondrial membrane potential, all three nucleosides caused a significant increase in cytosolic cytochrome c (p>0.05), with a corresponding decrease in mitochondrial cytochrome c. Morphological analysis of both cell lines showed the rapid appearance of vacuoles following exposure to two of the nucleosides, while a third caused cellular detachment, delayed cytoplasmic vacuolisation and nuclear abnormalities. Preliminary investigations, using the autophagic indicator monodansylcadaverine and chloroquine as positive control, showed that two of the nucleosides induced the formation of autophagic vacuoles. In summary, the novel nucleoside analogues showed selective cytotoxicity towards both cancer cell lines and are effective initiators of an unusual apoptotic response, demonstrating their potential to serve as structural scaffolds for more potent analogues.
Abnormal serum lipoprotein levels as a risk factor for the development of human lenticular opacities
(Clinics Cardiv Publishing, 2003-04) Meyer, D.; Parkin, D.; Maritz, F. J.; Liebenberg, P. H.
Aim: To determine whether an association exists between the different plasma lipoprotein constituents and the prevalence of lenticular opacities in dyslipidaemic subjects. Methods: Adult patients (n = 115) of both genders were included if their fasting total serum cholesterol concentrations exceeded the 95th percentile of normal or their serum low-density lipoprotein (LDL) : high-density lipoprotein (HDL) ratios exceeded 5. Patients were excluded if they suffered from any condition known to cause, or predispose them to, elevated lipoprotein levels or lenticular opacification. Lenticular changes were assessed by means of a slit-lamp through the fully dilated pupil. Results: An extremely strong association (p < 0.0001) was found to exist between HDL cholesterol levels and the development of lens opacities. Below an HDL-C level of 1.5 mmol/l subjects had a seven-fold higher calculated probability of falling in the lens opacity subgroup than those with HDL-C levels above 1.5 mmol/l [odds ratio = 7.33 (95% CI = 2.06–26.10; p = 0.001)]. An equally strong association was found between high (>5) LDL:HDL ratios and the development of lens opacities (p < 0.0003). The risk of falling into the cataract subgroup if the individual’s LDL:HDL ratio exceeded 5 was 2.35 (95% CI = 1.09–5.04; p = 0.014). Conclusions: This study strongly suggests that an association exists between low levels of HDL cholesterol and high LDL:HDL ratios on one hand and the development of adult lens opacification on the other.
Accelerating clinical evaluation of repurposed combination therapies for COVID-19
(American Society of Tropical Medicine and Hygiene, 2020-08-21) Rayner, Craig R.; Dron, Louis; Park, Jay J. H.; Decloedt, Eric H.; Cotton, Mark F.; Niranjan, Vis; Smith, Patrick F.; Dodds, Michael G.; Brown, Fran; Reis, Gilmar; Wesche, David; Mills, Edward J.
As the global COVID-19 pandemic continues, unabated and clinical trials demonstrate limited effective pharmaceutical interventions, there is a pressing need to accelerate treatment evaluations. Among options for accelerated development is the evaluation of drug combinations in the absence of prior monotherapy data. This approach is appealing for a number of reasons. First, combining two or more drugs with related or complementary therapeutic effects permits a multipronged approach addressing the variable pathways of the disease. Second, if an individual component of a combination offers a therapeutic effect, then in the absence of antagonism, a trial of combination therapy should still detect individual efficacy. Third, this strategy is time saving. Rather than taking a stepwise approach to evaluating monotherapies, this strategy begins with testing all relevant therapeutic options. Finally, given the severity of the current pandemic and the absence of treatment options, the likelihood of detecting a treatment effect with combination therapy maintains scientific enthusiasm for evaluating repurposed treatments. Antiviral combination selection can be facilitated by insights regarding SARS-CoV-2 pathophysiology and cell cycle dynamics, supported by infectious disease and clinical pharmacology expert advice. We describe a clinical evaluation strategy using adaptive combination platform trials to rapidly test combination therapies to treat COVID-19.
Angio-oedema associated with colistin
(Health & Medical Publishing Group, 2016) Abulfathi, A. A.; Greyling, T.; Makiwane, M.; Esser, M.; Decloedt, E.
ENGLISH ABSTRACT: A 50-year-old woman known to have type 1 diabetes mellitus presented with a rare case of angio-oedema associated with colistin use. The angio-oedema was temporally associated with the use and discontinuation of colistin with the reasonable exclusion of important differential diagnoses. Pseudoallergy may be a probable underlying mechanism. However, we cannot exclude the possibility of hereditary angio-oedema type 2 or 3, or that her concomitant medications (particularly enalapril) and her renal impairment contributed to the risk and severity of her angio-oedema.
Another look at erythromycin
(Health & Medical Publishing Group, 1978-04) Straughan, J. L.
ENGLISH ABSTRACT: The erythromycins are broadly reviewed from a clinical viewpoint. The antimicrobial spectrum, clinical indications, pharmacokinetics and toxicity are dealt with. The usefulness of erythromycin for respiratory tract infections is stressed. New evidence to support bactericidal activity of this antibiotic is noted. There seems little reason to use the potentially hepatotoxic estolate form of erythromycin. The safety of the other forms of this antibiotic available in this country is emphasized.
Application of Caco-2 cell line in herb-drug interaction studies : current approaches and challenges
(Canadian Society for Pharmaceutical Sciences, 2014-01) Awortwe, C.; Fasinu, P. S.; Rosenkranz, B.
The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes, transporters, microvilli and enterocytes of identical characteristics to the human small intestine. The FDA recommends this model as integral component of the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use the Caco-2 cell line to screen new chemical entities through prediction of its solubility, bioavailability and the possibility of drug-drug or herb-drug interactions in the gut lumen. However, challenges in the inherent characteristics of Caco-2 cell and inter-laboratory protocol variations have resulted to generation of irreproducible data. These limitations affect the extrapolation of data from pre-clinical research to clinical studies involving drug-drug and herb-drug interactions. This review addresses some of these caveats and enumerates the plausible current and future approaches to reduce the anomalies associated with Caco-2 cell line investigations focusing on its application in herb-drug interactions.
Artemisia Spp. derivatives for COVID-19 treatment : anecdotal use, political hype, treatment potential, challenges, and road map to randomized clinical trials
(American Society of Tropical Medicine and Hygiene, 2020) Kapepula, Paulin M.; Kabengele, Jimmy K.; Kingombe, Micheline; Van Bambeke, Francoise; Tulkens, Paul M.; Kishabongo, Antoine Sadiki; Decloedt, Eric; Zumla, Adam; Tiberi, Simon; Suleman, Fatima; Tshilolo, Leon; Muyembe-TamFum, Jean-Jacques; Zumla, Alimuddin; Nachega, Jean B.
The world is currently facing a novel COVID-19 pandemic caused by SARS-CoV-2 that, as of July 12, 2020, has caused a reported 12,322,395 cases and 556,335 deaths. To date, only two treatments, remdesivir and dexamethasone, have demonstrated clinical efficacy through randomized controlled trials (RCTs) in seriously ill patients. The search for new or repurposed drugs for treatment of COVID-19 continues. We have witnessed anecdotal use of herbal medicines, including Artemisia spp. extracts, in low-income countries, and exaggerated claims of their efficacies that are not evidence based, with subsequent political controversy. These events highlight the urgent need for further research on herbal compounds to evaluate efficacy through RCTs, and, when efficacious compounds are identified, to establish the active ingredients, develop formulations and dosing, and define pharmacokinetics, toxicology, and safety to enable drug development. Derivatives from the herb Artemisia annua have been used as traditional medicine over centuries for the treatment of fevers, malaria, and respiratory tract infections. We review the bioactive compounds, pharmacological and immunological effects, and traditional uses for Artemisia spp. derivatives, and discuss the challenges and controversies surrounding current efforts and the scientific road map to advance them to prevent or treat COVID-19.
Association between health-related quality of life and medication adherence in pulmonary tuberculosis in South Africa
(Frontiers Media, 2017-12-18) Kastien-Hilka, Tanja; Rosenkranz, Bernd; Schwenkglenks, Matthias; Bennett, Bryan M.; Sinanovic, Edina
Background: Health-related quality of life (HRQOL) and adherence to treatment are two often inter-related concepts that have implications for patient management and care. Tuberculosis (TB) and its treatment present a major public health concern in South Africa. The study aimed to evaluate the association between HRQOL and adherence in TB patients in South Africa. Methods: Four self-reported HRQOL and one self-reported adherence measures were used in an observational longitudinal multicentre study during 6-month standard TB treatment. These included the generic Short-Form 12 items (SF-12) and European Quality of Life 5 dimensions 5 levels (EQ-5D-5L), the disease-specific St. George's Respiratory Questionnaire (SGRQ) and the condition-specific Hospital Anxiety and Depression Scale (HADS) for HRQOL. Adherence was measured by the Morisky Medication Adherence Scale 8 items (MMAS-8). The relationship between both concepts was examined in 131 patients using Spearman's rho correlations, and linear regression models. Results: HRQOL improved over 6-month TB treatment, whereas adherence mean scores stayed constant with participants attaining a medium average level. Around 76% of patients reported to be high adherers and 24% were reporting a medium or low adherence. Associations between HRQOL and adherence were mainly weak. High adherence at treatment start was positively related to improvements in anxiety and depression after 6-month treatment. The overall improvement in pain and discomfort, and psychosocial health aspects over treatment time was positively, but weakly associated with adherence at 6 months of treatment. Conclusion: A positive relationship exists between adherence and HRQOL in TB in a South African setting, but this relationship was very weak, most likely because HRQOL is affected by a number of different factors and not limited to effects of adherence. Therefore, management of TB patients should, besides adequate drug treatment, address the specific mental and psychosocial needs.
B-cell and T-cell activation in South African HIV-1-positive non-Hodgkin’s lymphoma patients
(Medpharm Publications, 2018) Flepisi, Brian T.; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd
Background: Altered immune mechanisms play a critical role in the pathogenesis of non-Hodgkin’s lymphoma (NHL). HIV-1 (HIV) infection is associated with a state of excessive T-cell activation, which can lead to increased T-cell turnover and lymph node fibrosis. Objectives: This study aimed to determine the serum levels of circulating B-cell activation markers, and the expression of T-cell activation and regulatory markers in HIV-positive NHL patients. Method: The serum levels of circulating soluble(s) sCD20, sCD23, sCD27, sCD30 and sCD44 molecules, all of which are biomarkers of B-cell activation, were determined by enzyme-linked immunosorbent assays (ELISA), while biomarkers of T-cell activation (CD8+CD38+) and regulation (FoxP3) were determined by flow cytometry in 141 subjects who were divided into five groups: Combination antiretroviral therapy (ART)-naïve HIV-positive patients; ART-treated HIV-positive patients; HIV-negative NHL patients; HIV-positive NHL patients on ART; and healthy controls. Results: HIV-positive NHL patients had significantly higher serum levels of sCD20, sCD23, sCD30 and sCD44 than HIV-negative NHL patients, while all five biomarkers were significantly elevated in HIV-positive NHL patients when compared with ART-treated HIV-positive patients. HIV-positive NHL patients had higher CD8+CD38+ and lower FoxP3 expression than HIV-negative NHL and ART-treated HIV-positive patients. Conclusion: B-cell activation is increased in HIV-positive NHL patients and is associated with reduced regulatory T-cell populations and increased CD8+ T-cell activation.
Berg adder (Bitis atropos) : an unusual case of acute poisoning
(Health and Medical Publishing Group, 2017) Wium, C. A.; Marks, C. J.; Du Plessis, C. E.; Muller, G. J.
A 5-year-old boy presented to hospital with mild local cytotoxic and severe neurotoxic symptoms. The neurotoxic symptoms included ptosis, fixed dilated pupils and flaccid paralysis with respiratory failure. Mild hyponatraemia was also a clinical feature. After various unsuccessful treatment options were followed, the Tygerberg Poison Information Centre was contacted and a diagnosis of berg adder bite was made. Berg adder bites are uncommon and therefore not usually considered in the differential diagnosis of a patient presenting with an unexplained clinical picture. A timeous poison information helpline consultation is recommended in this situation.
Biomarkers of HIV-associated cancer
(Libertas Academica, 2014) Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd
Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin’s lymphoma, and invasive cervical cancer.
‘Building on shaky ground’—challenges to and solutions for primary care guideline implementation in four provinces in South Africa : a qualitative study
(BMJ Publishing, 2020-05) Kredo, Tamara; Cooper, Sara; Abrams, Amber Louise; Muller, Jocelyn; Schmidt, Bey-Marrié; Volmink, Jimmy; Atkins, Salla
Objectives Clinical guidelines support evidence-informed quality patient care. Our study explored perspectives of South African subnational health managers regarding barriers to and enablers for implementation for all available primary care guidelines. Design: We used qualitative research methods, including semistructured, individual interviews and an interpretative perspective. Thematic content analysis was used to develop data categories and themes. Setting: We conducted research in four of nine South African provinces with diverse geographic, economic and health system arrangements (Eastern Cape, Western Cape, KwaZulu-Natal, Limpopo). South Africa is a middle-income country with high levels of inequality. The settings represented public sector rural and peri-urban health facilities. Participants: Twenty-two participants with provincial and district health management roles, that comprised implementation and/or training on primary care guidelines, were included. Results: Participants recommended urgent consideration of health system challenges, particularly financial constraints, impacting on access to the guidelines themselves and to medical equipment and supplies necessary to adhere to guidelines. They suggested that overcoming service delivery gaps requires strengthening of leadership, clarification of roles and enhanced accountability. Participants suggested that inadequate numbers of skilled clinical staff hampered guideline use and, ultimately, patient care. Quality assurance of training programmes for clinicians—particularly nurses—interdisciplinary training, and strengthening post-training mentorship were recommended. Furthermore, fit-for-purpose guideline implementation necessitates considering the unique settings of facilities, including local culture and geography. This requires guideline development to include guideline end users. Conclusions: Guidelines are one of the policy tools to achieve evidence-informed, cost-effective and universal healthcare. But, if not effectively implemented, they have no impact. Subnational health managers in poorly resourced settings suggested that shortcomings in the health system, along with poor consultation with end users, affect implementation. Short-term improvements are possible through increasing access to and training on guidelines. However, health system strengthening and recognition of socio-cultural–geographic diversity are prerequisites for context-appropriate evidence-informed practice.
Chemical incompatibility of parenteral drug admixtures
(Health & Medical Publishing Group, 1974) McCarthy, T. J.
Incompatibilty of parenteral drug admixtures is a subject with such wide ramifications that the problem of correlating all the factors will in future probably only be controlled by computer techniques. In the meantime, a knowledge of pH factors and a sound reference library, together with a pre-planned use of drug combinations wherever possible, will do much to alleviate the problem. Useful reference articles and facets of pH are discussed. Consideration should be given to avoiding admixtures of undocumented drugs in infusion fluids, and use should be made of a single drug injection at a separate locus.
Chloroquine and hydroxychloroquine for the prevention or treatment of Novel Coronavirus Disease (COVID-19) in Africa : caution for inappropriate off-label use in healthcare settings
(American Society of Tropical Medicine and Hygiene, 2020) Abena, Pascale M.; Decloedt, Eric H.; Bottieau, Emmanuel; Suleman, Fatima; Adejumo, Prisca; Sam-Agudu, Nadia A.; TamFum, Jean-Jacques Muyembe; Seydi, Moussa; Eholie, Serge P.; Mills, Edward J.; Kallay, Oscar; Zumla, Alimuddin; Nachega, Jean B.
ENGLISH ABSTRACT: The novel severe acute respiratory syndrome-coronavirus-2 pandemic has spread to Africa, where nearly all countries have reported laboratory-confirmed cases of novel coronavirus disease (COVID-19). Although there are ongoing clinical trials of repurposed and investigational antiviral and immune-based therapies, there are as yet no scientifically proven, clinically effective pharmacological treatments for COVID-19. Among the repurposed drugs, the commonly used antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) havebecome the focus of global scientific, media, and political attention despite a lack of randomized clinical trials supporting their efficacy. Chloroquine has been used worldwide for about 75 years and is listed by theWHOas an essential medicine to treat malaria. Hydroxychloroquine is mainly used as a therapy for autoimmune diseases. However, the efficacy and safety of CQ/HCQ for the treatment of COVID-19 remains to be defined. Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations. Much needed in Africa is a cross-continental collaborative network for coordinated production, distribution, and post-marketing surveillance aligned to low-cost distribution of any approved COVID-19 drug; this would ideally be piggybacked on existing global aid efforts. Meanwhile, African countries should strongly consider implementing prescription monitoring schemes to ensure that any off-label CQ/HCQ use is appropriate and beneficial during this pandemic.
Clinical trials of disease stages in COVID 19 : complicated and often misinterpreted
(Elsevier, 2020-08-20) Park, Jay J. H.; Decloedt, Eric H.; Rayner, Craig R.; Cotton, Mark; Mills, Edward J.
As of July 28, 2020, 1840 clinical trials were registered globally, with 1001 clinical trials recruiting patients for COVID-19 management.1 Despite this large number, only 30 trials have been published as peer-reviewed or preprint publications.2 Media reports and prepublications on medRxiv and bioRxiv represent the most frequent mechanism for data sharing, with wide public reach and usually with little detail. However, with inadequate details on the trials and only superficial scrutiny by the public and scientific decision makers, the consequences have had disastrous effects on other clinical trial funding, permissions, recruitment, and interpretation.
The control of peroxidase-catalysed iodination and de-iodination
(Health & Medical Publishing Group, 1981) Van Zyl, A.; Burger, B.; Rossouw, P.; Wilson, B.
It has been demonstrated that the H2O2/l- ratio is a critical factor in the control of iodination and deiodination of covalently bound tyrosyl residues in proteins and free iodotyrosines by peroxidase enzymes. This has been shown for myeloperoxidase (MPO) isolated from normal human polymorphonuclear lymphocytes in particular, and also for peroxidases of animal origin such as thyroid peroxidase (TPO) and lactoperoxidase (LPO). It has also been shown that the H2O2/l ratio exerts a controlling influence on MPO-catalysed reactions of fully iodinated tyrosines, e.g. di-iodotyrosine, and of partially and completely iodinated thyronines such as thyroxine and tri-iodothyronine. Using an in vivo model system it has been shown that MPO catalyses the sequential events of iodination, iodine exchange and de-iodination of tyrosines and, furthermore, that all three reactions are influenced by the rate of H2O2 generation and the iodide concentration of the reaction medium. The action of MPO on iodothyronine substrates only affects de-iodination irrespective of whether the iodothyronine is partially iodinated, as in triiodothyronine, or completely iodinated, as in thyroxine. This MPO-catalysed de-iodination of thyroxine and tri-iodothyronine can also be regulated by the H2O2/l- ratio. Moreover, the results show that MPO-catalysed iodine exchange can only occur in completely iodinated tyrosines such as diiodotyrosine (DIT). Iodine exchange in partially iodinated tyrosines such as mono-iodotyrosine (MIT) or in iodothyronines (T3 and T4) cannot be catalysed by MPO irrespective of the H2O2/l- ratio. These results introduce a new concept which may be important in understanding the control of thyroid activity in thyroid disease and the control of MPO activity in biological defence mechanisms in man.
Coronary spasm and thrombosis in a bodybuilder using a nutritional supplement containing synephrine, octopamine, tyramine and caffeine
(Health and Medical Publishing Group (HMPG), 2008-05) Smedema, J. P.; Muller, G. J.
Current evidence for directed and supportive investigational therapies against COVID-19
(Health & Medical Publishing Group, 2020-04-30) Van Rensburg, R.; Pillay-Fuentes Lorente, V.; Decloedt, E. H.
ENGLISH ABSTRACT: Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.

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