A framework for the use of biological medicines in the free state province, South Africa.

Purpose: The use of biological medicines (BM) has increased worldwide owing to their effectiveness in the treatment of many chronic diseases. However, in South Africa, access to BM remains limited, hence, there is a need to develop strategies that will enable timely access to BM by all patients who need them.

Objective: To develop a framework for the use of BM in South Africa.

Clinical Characteristics of Children with HIV Initiated on Antiretroviral Treatment at HIV Clinics in Bloemfontein, South Africa.

Background And Objective: Over the past 15 years, there have been three major updates to the South African national guidelines for the management of human immunodeficiency virus (HIV) in children. The purpose of this study is to describe the clinical characteristics of children who were initiated on antiretroviral therapy (ART) in Bloemfontein, South Africa, following these national treatment guidelines.

Methods: Clinical information during initiation of ART in children aged 0-13 years was obtained from five HIV clinics in Bloemfontein from 2004 to 2019 as part of the establishment of an antiretroviral (ARV) pediatric registry at the University of the Free State.

The development and use of a drug-induced immunosuppressed rat-model to screen Phela for mechanism of immune stimulation.

Ethnopharmacology Relevancy: Phela, is code name for a medicinal product made from four South African traditional medicinal plants (Clerodendrum glabrum E. Mey, Polianthes tuberosa (Linn.), Rotheca myricoides (Hochst.

Changes in IL-2 and IL-10 during Chronic Administration of Isoniazid, Nevirapine, and Paracetamol in Rats.

The aim of this study was to illustrate the initial subclinical drug-induced liver injury and the associated adaptive immune response by monitoring for the changes in plasma IL-2, IL-10, and some cytochrome P450 activity during chronic administration of nevirapine (NVP), isoniazid (INH), and paracetamol (PAR) in rats without clinical hepatotoxicity. Male Sprague-Dawley (SD) rats were divided into four groups (saline (S), NVP, INH, and PAR) of 25 animals each. The drugs were administered daily for 42 days at therapeutic doses (NVP 200 mg/kg, PAR 500 mg/kg, and INH 20 mg/kg) to the respective groups by oral gavage and five rats per group were sacrificed weekly.

Co-administration of fresh grape fruit juice (GFJ) and bergamottin prevented paracetamol induced hepatotoxicity after paracetamol overdose in rats.

The aim of this study was to evaluate small doses of known cytochrome P450 enzyme inhibitors, grapefruit juice (GFJ) and one of its components, bergamottin (BGT), for the prevention of paracetamol (PAR)-induced hepatotoxicity after overdose in rats. Six groups of 15 Sprague Dawley (SD) rats each were treated with single oral doses of either saline, PAR only 1725 mg/kg, PAR + GFJ low dose (2 ml) and PAR + GFJ high dose (3 ml), PAR + BGT 0.05 mg/kg (BGT-low) and PAR + BGT 0.

The current status and trend of clinical pharmacology in developing countries.

Background: Several international forums for promoting clinical pharmacology in developing countries have been held since 1980, and several clinical pharmacology programmes targeting developing countries were instituted such that the status of clinical pharmacology in developing countries is not where it was 50 years ago. Therefore, a survey and an appraisal of the literature on the current status of clinical pharmacology in developing countries were undertaken with a hope that it would enable development of appropriate strategies for further promotion of clinical pharmacology in these countries.

Methods: First, nine determinants (or enabling factors) for running a successful clinical pharmacology programme were identified, i.

Clinical pharmacology becomes a specialty in South Africa.

South Africa recently became the first African country where clinical pharmacology has been approved as a specialty. This article outlines the need for clinical pharmacologists, their role in advancing public health, the potential benefits to the country, and recommendations for ensuring a healthy future for the discipline.

The role of the immune system in nevirapine-induced subclinical liver injury of a rat model.

In this study, the role of the immune system in nevirapine- (NVP-) induced subclinical liver injury was investigated by observing for changes of some immune parameters during the initial stages of NVP-induced hepatotoxicity in a rat model. In the acute phase, two test-groups of 10 Sprague-Dawley rats each were administered with bacterial lipopolysaccharide (LPS) or saline (S) intraperitoneally, followed by oral NVP, after which 5 rats from each group were sacrificed at 6 and 24 hours. For the chronic phase, two groups of 15 rats each received daily NVP, and on days 7, 14, and 21, five rats from each group were administered with either LPS or S, followed by that day's NVP dose, and were sacrificed 24 hours later.

Evaluation of traditional medicines II: the use of metabolite peak-kinetics to monitor PHELA in rat plasma.

PHELA is a herbal mixture of four African traditional medicinal plants that is under development by the Medical Research Council (MRC) for use as an immune stimulant in immune compromised individuals. Before major in vivo investigations could be conducted, there was a need to establish a plasma marker for concentration monitoring of PHELA. Chromatographic separation was achieved using a C18 RP column (250 mm × 4.

Evaluation of traditional medicines III: the mechanism of immune modulation by PHELA.

PHELA is a herbal traditional medicine that is under development for use as an immune booster in immune compromised individuals. Therefore, the aim of this study was to determine PHELA's mechanism of action by observing for changes in cytokine profiles. Four groups of Sprague Dawley rats (n = 8) were treated daily and separately with normal-saline, cyclosporine-A, PHELA-only and PHELA+ cyclosporine-A.

Evaluation of traditional medicines I: identification of PHELA using different chromatographic techniques.

PHELA is a herbal mixture of four African traditional medicinal plants that has been used for decades in wasting conditions and is now being developed by the Medical Research Council (MRC) as an immune booster for patients with compromised immune system. A chromatographic fingerprint of PHELA was needed for quality control purposes. Here, a comprehensive method for fingerprinting of PHELA using different chromatographic techniques is described.

The effect of isoniazid containing regimen on CYP2E1 during antituberculosis therapy.

Because isoniazid is a selective inducer of CYP2E1 and isoniazid-induced hepatotoxicity is believed to be due to activation of its metabolites by CYP450, this study was undertaken to determine the effect of isoniazid containing regimen on CYP2E1 in TB-patients. The activity of CYP2E1 in 11 newly diagnosed TB-patients (5 F, 6 M) was investigated before (day 0) and during (day 14) treatment for tuberculosis. CYP2E1 activity was measured using the plasma metabolic ratio (MR) of 6-hydroxy-chlorzoxazone to chlorzoxazone, while CYP2E1 quantity in the peripheral lymphocytes was measured using SDS-PAGE.

Interaction between valproic acid and acyclovir after intravenous and oral administration in a rabbit model.

This study was undertaken to investigate the effect of co-administration of valproic acid and acyclovir on the pharmacokinetic parameters of each other. Fifteen white New Zealand rabbits were divided into three groups: A, B and C. Group A received acyclovir only, group B received valproic acid only and group C received a combination of acyclovir and valproic acid.

The role of cytochrome P450 in antiretroviral drug interactions.

As millions of patients with HIV/AIDS are put on treatment with the highly active antiretroviral therapy (HAART), drug interactions have become a major concern for healthcare providers. The use of HAART as a combination of 3 - 4 drugs creates potential for antiretroviral (ARV) drug interactions, and this is complicated by the addition of other drugs for treatment of other ailments such as comorbid chronic conditions and/or opportunistic infections. It has been observed that most ARV drug interactions involve drugs that interact with CYP enzymes.

RAT CYP3A and CYP2B1/2 were not associated with nevirapine-induced hepatotoxicity.

Nevirapine is an antiretroviral drug that is used for treatment as well as for the prevention of mother-to-child transmission of the human immunodeficiency virus (HIV). Unfortunately, its adverse effects, mainly hypersensitivity skin reactions and hepatotoxicity, have hampered the use of nevirapine. Since nevirapine-induced hepatotoxicity commonly occurs between 2-12 weeks of treatment, and nevirapine is a known inducer of human CYP3A and CYP2B6 isozymes, it was envisaged that the hepatotoxicity was due to activation of nevirapine to toxic metabolites by the induced enzymes.

The effect of surface charge on the disposition of liposome-encapsulated gentamicin to the rat liver, brain, lungs and kidneys after intraperitoneal administration.

The disposition of gentamicin to the normal rat brain, lung, kidney and liver was studied at intervals of 1, 2, 4, 6 and 8h after intraperitoneal injection of gentamicin encapsulated in positive, negative and neutral liposomes. Compared with the control, which was treated with free gentamicin, liposomes were associated with higher concentrations of gentamicin in the brain and liver, while concentrations were lower in the kidney. The average concentrations of gentamicin in the liver and the brain were highest with positive liposomes, while, gentamicin concentrations in the kidneys and lungs were not influenced by surface charge of the liposomes.

The role of cytochrome-P450 inhibitors in the prevention of hepatotoxicity after paracetamol overdose in rats.

Despite the understanding that some cytochrome P450 isoforms are responsible for activation of paracetamol to the hepatotoxic metabolite, N-acetyl-p-benzoquinineimine (NAPQI), the use of enzyme inhibitors for prevention and/or treatment of paracetamol hepatotoxicity is still not well researched. Here, a mixture of ketoconazole, isoniazid and caffeine (inhibitor solution), known inhibitors of CYP3A, CYP2E1 and CYP1A2, was investigated for prevention of hepatotoxicity after paracetamol over-dose in rats. The appropriate doses of paracetamol (1000 mg/kg/day) and the 'inhibitor solution' (ketoconazole 5 mg/kg, isoniazid 5 mg/kg and caffeine 10 mg/kg; =KIC-5-50), were selected in preliminary experiments.

A model for selecting assessment methods for evaluating medical students in African medical schools.

Introduction of more effective and standardized assessment methods for testing students' performance in Africa's medical institutions has been hampered by severe financial and personnel shortages. Nevertheless, some African institutions have recognized the problem and are now revising their medical curricula, and, therefore, their assessment methods. These institutions, and those yet to come, need guidance on selecting assessment methods so as to adopt models that can be sustained locally.

Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity.

Adequate bile flow, maintained in part by the efficient enterohepatic recirculation of bile acids, is critical for normal liver function. One important component of this process is the uptake of bile acids from the portal circulation into hepatocytes by the bile acid uptake transporter sodium taurocholate cotransporting polypeptide (NTCP). Thus, the expression and functional activity of this transporter may affect the rate of bile acid removal from the portal circulation.

The role of oxygen free radicals in isoniazid-induced hepatotoxicity.

Isoniazid and its metabolites acetylisoniazid, hydrazine and monoacetylhydrazine were investigated for generation of oxygen free radicals during incubation with rat liver slices. Lipid peroxidation was assessed by the thiobarbituric acid reactive substances test using malonaldehyde as the external standard, while hepatotoxicity was assessed by histopathology studies. Malonaldehyde formed in liver slices after 10 hours of incubation with the drugs was 1.

Phenytoin toxicity due to concomitant antituberculosis therapy.

Isoniazid inhibits the metabolism of phenytoin. Slow acetylators, who comprise roughly 50% of the South African population, are likely to develop clinical and biochemical features of phenytoin toxicity when this drug is given together with antituberculosis therapy. We describe a patient in whom this interaction caused a series of dangerous clinical events.