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

Correlation between different PBL assessment components and the final mark for MB ChB III at a rural South African university

Background. Problem-based learning (PBL) is now an accepted component of many medical school programmes worldwide. Our university also follows the PBL ‘SPICES’ model for MB ChB III. The assessment modalities used are the modified essay questions (MEQ), objective structured practical examination (OSPE), individualised process assessment (IPA) and tutorial continuous assessment (TUT). This study was done to compare the students’ performances in individual assessment components with the final mark to determine the correlation between these parameters. Materials and methods. The study was retrospective, descriptive and analytical, based on the integrated marks of all the MB ChB III students at Walter Sisulu University (WSU) in 2007. Assessment marks were stratified according to blocks and different types of assessment (MEQ, TUT, OSPE, IPA). Regression analysis was used to compute and scrutinise these vis-à-vis their correspondence with the final marks for each block. Results. Three hundred and seventy-nine block assessment marks of 96 students from 4 blocks of MB ChB III were analysed and the correlation between the assessment components and final mark were compared. Regression analysis showed good correlation when analysing the assessment modality versus the final mark for the MEQs (r=0.93, 0.93, 0.94, 0.96), followed by OSPEs (r=0.71, 0.70, 0.76, 0.77) and IPAs (r=0.62, 0.51, 0.68, 0.77). However, correlation was not significant with the TUT. Conclusion. There was good correlation between the students’ performance in the majority of assessment modalities and the final mark in the different blocks of the MB ChB III examination. There may be a need to make tutorial assessment methods more objective, partly by additional tutor training

Thermoelectric properties of the degenerate Hubbard model

We investigate the thermoelectric properties of a system near a pressure driven Mott-Hubbard transition. The dependence of the thermopower and the figure of merit on pressure and temperature within a degenerate Hubbard model for integer filling n=1 is calculated using dynamical mean field theory. Quantum Monte Carlo method is used to solve the impurity model. Obtained results can qualitatively explain thermoelectric properties of various strongly correlated materials.Comment: RevTex, 7 pages, 6 figure

Pridopidine selectively occupies sigma-1 rather than dopamine D2 receptors at behaviorally active doses

Dopamine stabilizers have stimulatory actions under low dopamine tone and inhibitory actions under high dopamine tone without eliciting catalepsy. These compounds are dopamine D-2 receptor (D2R) antagonists or weak partial agonists and may have pro-mnemonic and neuroprotective effects. The mechanism underlying their stimulatory and neuroprotective actions is unknown but could involve sigma-1R binding. The present study examined sigma-1R and D2R occupancy by the dopamine stabilizer pridopidine (ACR16) at behaviorally relevant doses in living rats. Rats were administered 3 or 15 mg/kg pridopidine, or saline, before injection of the radiotracer C-11-SA4503 (sigma-1R) or C-11-raclopride (D2R). Some animals received 60 mg/kg pridopidine and were only scanned with C-11-raclopride. Cerebral C-11-SA4503 binding was quantified using metabolite-corrected plasma input data and distribution volume (V (T)) calculated by Logan graphical analysis. C-11-raclopride binding was quantified using striatum-to-cerebellum ratios and binding potentials calculated with a simplified reference tissue model. Cunningham-Lassen plots indicated sigma-1R occupancies of 57 +/- 2 and 85 +/- 2 % after pretreatment of animals with 3 and 15 mg/kg pridopidine. A significant (44-66 %) reduction of C-11-raclopride binding was only observed at 60 mg/kg pridopidine. At doses shown to elicit neurochemical and behavioral effects, pridopidine occupied a large fraction of sigma-1Rs and a negligible fraction of D(2)Rs. Significant D2R occupancy was only observed at a dose 20-fold higher than was required for sigma-1R occupancy. The characteristics of dopamine stabilizers may result from the combination of high sigma-1R and low D2R affinity

The amyloid-β1-42-oligomer interacting peptide D-AIP possesses favorable biostability, pharmacokinetics, and brain region distribution.

We have previously developed a unique 8-amino acid Aβ42 oligomer-Interacting Peptide (AIP) as a novel anti-amyloid strategy for the treatment of Alzheimer's disease. Our lead candidate has successfully progressed from test tubes (i.e., in vitro characterization of protease-resistant D-AIP) to transgenic flies (i.e., in vivo rescue of human Aβ42-mediated toxicity via D-AIP-supplemented food). In the present study, we examined D-AIP in terms of its stability in multiple biological matrices (i.e., ex-vivo mouse plasma, whole blood, and liver S9 fractions) using MALDI mass spectrometry, pharmacokinetics using a rapid and sensitive LC-MS method, and blood brain barrier (BBB) penetrance in WT C57LB/6 mice. D-AIP was found to be relatively stable over 3 h at 37 °C in all matrices tested. Finally, label-free MALDI imaging showed that orally administered D-AIP can readily penetrate the intact BBB in both male and female WT mice. Based upon the favorable stability, pharmacokinetics, and BBB penetration outcomes for orally administered D-AIP in WT mice, we then examined the effect of D-AIP on amyloid "seeding" in vitro (i.e., freshly monomerized versus preaggregated Aβ42). Complementary biophysical assays (ThT, TEM, and MALDI-TOF MS) showed that D-AIP can directly interact with synthetic Aβ42 aggregates to disrupt primary and/or secondary seeding events. Taken together, the unique mechanistic and desired therapeutic potential of our lead D-AIP candidate warrants further investigation, that is, testing of D-AIP efficacy on the altered amyloid/tau pathology in transgenic mouse models of Alzheimer's disease

Magnetic Phase Diagram and Metal-Insulator Transition of NiS2-xSex

Magnetic phase diagram of NiS2-xSex has been reexamined by systematic studies of electrical resistivity, uniform magnetic susceptibility and neutron diffraction using single crystals grown by a chemical transport method. The electrical resistivity and the uniform magnetic susceptibility exhibit the same feature of temperature dependence over a wide Se concentration. A distinct first order metal-insulator (M-I) transition accompanied by a volume change was observed only in the antiferromagnetic ordered phase for 0.50<x<0.59. In this region, the M-I transition makes substantial effects to the thermal evolution of staggered moments. In the paramagnetic phase, the M-I transition becomes broad; both the electrical resistivity and the uniform magnetic susceptibility exhibit a broad maximum around the temperatures on the M-I transition-line extrapolated to the paramagnetic phase.Comment: 6 pages, 8 figures, corrected EPS fil