Johannes Bodenstein

N-terminal residues control proteasomal degradation of RGS2, RGS4, and RGS5 in human embryonic kidney 293 cells.

Regulator of G protein signaling (RGS) proteins modulate G protein-coupled receptor (GPCR) signaling. The N termini of some RGS4-family proteins provide receptor specificity and also contain an N-end rule determinant that results in ubiquitylation and decreased protein expression. The relevance of these mechanisms to other RGS proteins is not fully understood. Thus we examined function, receptor specificity, and expression of R4 subfamily RGS proteins (RGS2, -3, -4, -5, and -8). Although the N terminus plays a key role in protein stability in human embryonic kidney (HEK) 293 cells, we were unable to demonstrate specificity of RGS2, -3, -4, -5, or -8 for muscarinic receptors (M1, M3, and M5). However, cellular RGS activity (8 = 3 > 2) was strongly correlated with expression; RGS4 and -5 had minimal expression and activity. Stabilizing mutations of RGS4 and -5 (C2S) enhanced expression and function with a greater influence on RGS4 than on RGS5. We were surprised to find that a predicted destabilizing mutation in RGS8 (A2C) did not markedly affect expression and had no effect on function. In contrast, a destabilizing mutation in RGS2 (RGS2-Q2L) recently identified as a rare N-terminal genetic variant in a Japanese hypertensive cohort (J Hypertens 23:1497–1505, 2005) showed significantly reduced expression and inhibition of angiotensin II (AT1) receptor-stimulated accumulation of inositol phosphates. We were surprised to find that RGS2-Q2R, also predicted to be destabilizing, showed nearly normal expression and function. Thus, proteasomal regulation of RGS expression in HEK293 cells strongly controls RGS function and a novel RGS2 mutation with decreased protein expression could be relevant to the pathophysiology of hypertension in humans.

The chemical structures, plant origins, ethnobotany and biological activities of homoisoflavanones

This work reviews the four basic structural types of homoisoflavanones. The relationships between the various structures of homoisoflavanones and their plant origins, ethnobotany and biological activities are put into perspective.

An investigation of the antimicrobial and anti-inflammatory activities of crocodile oil.

ETHNOPHARMACOLOGICAL RELEVANCE Crocodile oil has been used by traditional practitioners world-wide to treat microbial infections and inflammatory conditions. However, the scientific rationale behind its use is not completely understood. This study provides an updated fatty acid profile and novel scientific evidence of the antimicrobial and anti-inflammatory properties of crocodile oil, obtained from the Nile crocodile (Crocodylus niloticus), justifying its use by traditional healers. MATERIALS AND METHODS The fatty acid content of the oil was determined by gas chromatography and the major fatty acids were identified. A microplate method was used to assess activity of the oil against Staphylococcus aureus, Klebsiella pneumoniae and Candida albicans. The anti-inflammatory activity of the oil was assessed by oral administration and topical application, utilising a mouse model of acute croton oil-induced contact dermatitis. RESULTS Sixteen fatty acids were identified with oleic, palmitic and linoleic acid being the major components of the oil. The optimal activity of the oil against the bacteria and fungus was obtained with 15% and 6% (w/v) oil respectively. No significant selectivity was observed against the bacterial species, but Candida albicans was more susceptible. The anti-inflammatory assays showed optimal activity at 3h after the oral administration of oil (60.8±5.5%) and at 12h after topical application (57.5±5.9%). This suggested a short duration of action when the oil was orally administered, and a longer duration of action when it was topically applied. CONCLUSIONS Subsequent studies may be directed towards the investigation of the mechanisms of action of the antimicrobial and anti-inflammatory activities of crocodile oil and its fatty acids.

Quality teaching and learning in the Health Sciences

Quality teaching is a central tenet to the retention and success of students in higher education but teaching quality measures and indicators have not enjoyed sufficient debate and discourse within the higher education sector. The Faculty of Health Sciences at the University of KwaZulu-Natal investigated the use of various programme and module statistics as well as student and peer evaluations of teaching to inform quality improvements in teaching and learning. Quantitative data allowed benchmarking in relation to internal University targets and national norms and pointed to the student cohorts who collectively required teaching and learning interventions but was found to have limited use in improving individual teaching practice. Qualitative data from students and peers was best able to highlight strengths and weaknesses and provided the most useful data to inform changes in teaching practice as it engendered and enhanced reflective practice. The Organization for Economic Co-operation and Development (OECD) report on quality teaching in higher education found that most evaluation instruments were related to teaching input indicators and that there was a dearth of instruments to evaluate the impact of teaching, i.e. there was no explicit evaluation criteria linking teaching input to learning outcome. The challenge for the second cycle of institutional reviews/audits will thus be (1)identifying suitable qualitative indicators/measures for quality teaching , (2) striking the correct balance between quantitative and qualitative teaching quality indicators/measures, and (3), ensuring that such indicators, both quantitative/qualitative address teaching impact/learning outcomes in addition to teaching inputs.

Anti-inflammatory activities of selected synthetic homoisoflavanones

Four homoisoflavanones of the 3-benzylidene-4-chromanone type, some of which were previously isolated from Caesalpinia pulcherrima, were synthesised to determine their anti-inflammatory activity and cytotoxicity. A range of four different homoisoflavanones (compounds 4a–4d) were synthesised from the corresponding substituted phenols.1H- and 13C-NMR data together with high-resolution mass spectroscopy data were employed to elucidate the structures. Anti-inflammatory activity was determined in mice with acute croton oil-induced auricular dermatitis. In vitro cytotoxicity was tested against a Chinese hamster ovarian cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Compound 4a exhibited a tendency to inhibit oedema in a dose-dependent manner after 3 and 6 h of treatment. Compounds 4b–4d also inhibited oedema, although a clear dose-response relationship was not observed. Compounds 4a–4c were found to be less cytotoxic than compound 4d. Compound 4b was the least cytotoxic. Compounds 4a–4d exhibited anti-inflammatory activity and varying levels of cytotoxicity.

The cytotoxic effects of Scilla nervosa (Burch.) Jessop (Hyacinthaceae) aqueous extract on cultured HepG2 cells

ETHNOPHARMACOLOGICAL RELEVANCE Bulbs of Scilla nervosa, a medicinal plant indigenous to Southern Africa, are traditionally used in aqueous decoctions to treat a diverse range of illnesses. The bulbs contain homoisoflavanones and stilbenoids. Little information is known about the plants toxicity on the liver, a major detoxifying organ. This study investigated the effects of an aqueous extract of the bulbs in cultured HepG2 liver cells, a model system for investigating the toxicity of xenobiotics. MATERIALS AND METHODS The concentration that reduced cell viability to 50% (IC(50)) after 24h treatment was derived. Potential mechanisms of toxicity using the IC(50) were investigated as changes in metabolic activity, apoptosis, oxidative damage and DNA fragmentation. In addition, cytochrome P450 3A4 (CYP3A4) activity, which is implicated in drug metabolism and interactions, was also assayed. RESULTS Cell viability decreased in a concentration-dependent manner and the IC(50) was determined as 0.03 mg/mL. Treating the cells at the IC(50) for 24h resulted in increased intracellular ATP levels, no significant change in phosphatidylserine externalisation, increased caspase-8 activity, decreased caspase-9 activity, no significant change in mitochondrial membrane potential, increased lipid peroxidation, evidence for genotoxicity as demonstrated by DNA fragmentation, and slightly induced CYP3A4 activity. CONCLUSION Results suggest that liver cells are sensitive to an aqueous extract of the bulbs and there is an increased potential to induce apoptosis, oxidative stress and genotoxicity in vitro.

Use of concomitant medication in the treatment of schizophrenia

Schizophrenia is a life-long disorder that requires continuous pharmacotherapy. About 10 to 30% of patients with schizophrenia show poor response to antipsychotic medication alone, therefore concomitant medication is often used. The rationale for the addition of concomitant medication is often unclear and based on limited evidence. The most frequently prescribed concomitant medications in the treatment of schizophrenia include anticholinergic medication, antidepressants, anxiolytics for example, benzodiazepines, lithium and anticonvulsant medication for example, valproex. Indications for adding these medications to antipsychotic treatment regimens vary from controlling specific symptoms associated with schizophrenia for example, anxiety symptoms, aggressive behavior and suicidality, to managing adverse effects for example, parkinsonian side effects caused by antipsychotic medication. Although there is a need for concomitant medication in the treatment of schizophrenia, each patient needs to be assessed individually since the use of concomitant medication can also have negative treatment implications, for example an increase in the occurrence of adverse effects and drug interactions. Due to the diversity of the disease profile of schizophrenia, no one adjunctive treatment benefits all patients, therefore the choice of specific treatment is best guided by the clinical characteristics and presentation of the individual patient. The aim of this paper is thus to present a qualitative review of the literature. Key words: Schizophrenia, concomitant medication, antipsychotics, anticholinergics, antidepressants.

3-Bromo­chroman-4-one

The heterocyclic ring of the title compound, C9H7BrO2, obtained by bromination of 4-chromanone with copper bromide, adopts a half-chair conformation. The supramolecular structure is governed by a weak C—H⋯O hydrogen bond. There is also π–π stacking between symmetry-related benzene rings; the centroid–centroid distance is 3.9464 (18), the perpendicular distance between the rings is 3.4703 (11) and the offset is 1.879 Å.

The Susceptibility of Staphylococcus aureus and Klebsiella pneumoniae to Naturally Derived Selected Classes of Flavonoids

The emergence of multi-drug resistant organisms has increasingly become a global public health issue. Rational and appropriate uses of antibiotics as well as strict infection control measurements are recommended in order to reduce the emergence of antibiotic resistant bacteria (Tseng et al., 2011). The complexity in treating multi-drug resistant infections has led to an increase in the search for novel and effective antibiotics, especially structures originating from natural products. Promising molecules could serve as lead compounds to be developed and researched further.

Antiretroviral prescriptions with potential drug-drug interactions from general practitioners and specialists.

1with about 5 million of them living in South Africa (SA). The World Health Organization estimated that 4.7 million people living in sub-Saharan Africa urgently needed antiretroviral therapy (ART). In that year SA implemented prescribed minimum benefits (PMBs) for HIV/AIDS in the private health care sector. 2 Despite the increased availability and affordability of ART in SA, only 60 000 people were receiving ART through medical aid schemes by mid-2005. 3 Antiretrovirals (ARVs) have transformed HIV/AIDS into a chronic disorder that can be managed effectively. The right of all HIVinfected adults and children to receive standard care is endorsed by the SA HIV Clinicians Society (SAHIVCS), 4 with ART guidelines recommending different combinations. The rapid approval of new drugs resulted in an increased risk of prescribing errors, dispensing of incorrect dosages/dose frequencies, and incorrect reporting of drugs by the patient to the prescribers, 5 all leading to treatment failure. Drug-drug interactions (DDIs) are an under-recognised consequence of medication prescription errors, resulting in significant health care costs. 6 Since DDIs determine positive and negative consequences of treatment for HIV-infected patients, recommendations to avoid some drug combinations and to adjust dosages of some co-administered drugs were formulated by both the SAHIVCS 4