South African Dyslipidaemia Guideline Consensus Statement: A joint statement from the South African Heart Association (SA Heart) and the Lipid and Atherosclerosis Society of Southern Africa (LASSA)

The European Society of Cardiology together with the European Atherosclerosis Society published updated dyslipidaemia guidelines in 2011. SA Heart and the Lipid and Atherosclerosis Society of Southern Africa officially adopt these guidelines. This statement adapts aspects of the guidelines to the South African situation. Using the updated Framingham risk charts, interventional strategies are based according to the cardiovascular risk score and low-density lipoprotein cholesterol (LDL-C) levels. The Framingham risk score refers to the 10-year risk of any cardiovascular event, and includes four categories of risk. Treatment targets are those of the European guidelines. The LDL-C goal is 1.8 mmol/l for the very high-risk group (>30%), 2.5 mmol/l for the high-risk group (15 - 30%), and 3 mmol/l for those below 15% risk. Intensive management of dyslipidaemia in South Africa will significantly reduce the cardiovascular disease health burden

South African dyslipidaemia guideline consensus statement

The European Society of Cardiology together with the European Atherosclerosis Society published updated dyslipidaemia guidelines in 2011. SA Heart and the Lipid and Atherosclerosis Society of Southern Africa officially adopt these guidelines. This statement adapts aspects of the guidelines to the South African situation. Using the updated Framingham risk charts, interventional strategies are based according to the cardiovascular risk score and low-density lipoprotein cholesterol (LDL-C) levels. The Framingham risk score refers to the 10-year risk of any cardiovascular event, and includes four categories of risk. Treatment targets are those of the European guidelines. The LDL-C goal is 1.8mmol/l for the very high-risk group (>30%), 2.5mmol/l for the high-risk group (15 - 30%), and 3mmol/l for those below 15% risk. Intensive management of dyslipidaemia in South Africa will significantly reduce the cardiovascular disease health burden

In Vitro and In Vivo Efficacy of a Novel and Long-Acting Fungicidal Azole, PC1244, on Aspergillus fumigatus Infection

The antifungal effects of the novel triazole, PC1244, designed for topical or inhaled administration, againstA. fumigatushave been tested in a range ofin vitroandin vivostudies. PC1244 demonstrated potent antifungal activities against clinicalA. fumigatusisolates (N=96) with a MIC range of 0.016--0.25 μg/ml, whereas the MIC range for voriconazole was 0.25--0.5 μg/ml. PC1244 was a strong tight-binding inhibitor of recombinantA. fumigatusCYP51A and CYP51B (sterol 14α-demethylase) enzymes and strongly inhibited ergosterol synthesis inA. fumigatuswith an IC50of 8 nM. PC1244 was effective against a broad spectrum of pathogenic fungi (MIC ranged from <0.0078∼2 μg/ml), especially onAspergillus terreus,Trichophyton rubrum,Candida albicans,Candida glabrata,Candida krusei,Cryptococcus gattii,Cryptococcus neoformans and Rhizopus oryzaePC1244 also proved to be quickly absorbed into bothA. fumigatushyphae and bronchial epithelial cells, producing persistent antifungal effects. In addition, PC1244 showed fungicidal activity (MFC, 2 μg/ml), which was 8-fold more potent than voriconazole.In vivo, once daily intranasal administration of PC1244 (3.2 ∼ 80μg/mL) to temporarily neutropenic, immunocompromised mice 24h after inoculation with itraconazole-susceptibleA. fumigatussubstantially reduced fungal load in the lung, galactomannan in serum and circulating inflammatory cytokines. Furthermore, 7 days extended prophylaxis with PC1244 showed superiorin vivoeffects when compared against 1 day of prophylactic treatment, suggesting accumulation of the effects of PC1244. Thus, PC1244 has the potential to be a novel therapy for the treatment ofA. fumigatusinfection in the lungs of humans

The effects of serum, lithium, ethacrynic acid, and a low external concentration of potassium on specific [3H]-ouabain binding to human lymphocytes after incubation for 3 days.

We have quantified specific [3H]-ouabain binding sites in normal human lymphocytes, and have measured the changes in the numbers of those sites which occur in response to various stimuli. We have confirmed previous findings that incubation for 72 h in the presence of fetal calf serum causes an increase in [3H]-ouabain binding, and that this does not occur if the cells are incubated in fetal calf serum which has first been dialysed. During incubation of the lymphocytes for 3 days in the presence of dialysed fetal calf serum each of the following stimuli caused an increase in specific [3H]-ouabain binding: addition of ethacrynic acid (1 mumol l-1), addition of lithium (1 mmol l-1), and reduction of the external potassium concentration (to 0.75 mmol l-1). By analogy with the similar results in HeLa cells reported by others, we suggest that the increase in [3H]-ouabain binding may, in the case of ethacrynic acid and the reduction of the external potassium concentration, be initiated by an increase in the intracellular sodium concentration. The mechanisms whereby fetal calf serum and lithium cause an increase in [3H]-ouabain binding are not clear

Combining fMRI with a pharmacokinetic model to determine which brain areas activated by painful stimulation are specifically modulated by remifentanil.

We present a method for investigating the dynamic pharmacological modulation of pain-related brain activity, measured by BOLD-contrast fMRI. Noxious thermal stimulation was combined with a single infusion and washout of remifentanil, a short-acting opioid analgesic agent. The temporal profile of the effect site concentration of remifentanil, estimated from a pharmacokinetic model, was incorporated into a linear model of the fMRI data. The methodology was tested in nine healthy male subjects. During each imaging session the subjects received noxious thermal stimulation to the back of the left hand, prior to infusion, during infusion to a remifentanil effect site concentration of 1.0 ng/ml, and during washout of the remifentanil. Infusions were repeated with saline. Remifentanil-induced analgesia was confirmed from subjective pain intensity scores. Pain-related brain activity was identified in a matrix of regions using a linear model of the transient BOLD responses to noxious stimulation. Of those regions, there was a significant fractional reduction in the amplitude of the pain-related BOLD response in the insular cortex contralateral to the stimulus, the ipsilateral insular cortex, and the anterior cingulate cortex. Statistical parametric mapping of the component of pain-related BOLD responses that was linearly scaled by remifentanil concentration confirmed the contralateral insular cortex as the pain-processing region most significantly modulated by remifentanil compared to saline. The mapping of specific modulation of pain-related brain activity is directly relevant for understanding pharmacological analgesia. The method of examining time-dependent pharmacological modulation of specific brain activity may be generalized to other drugs that modulate brain activity other than that associated with pain