Prevalence of drug-drug interactions of antiretroviral agents in the private health care sector in South Africa

Objectives. Human immunodefiency virus (HIV) infection can be effectively treated with highly active antiretroviral therapy (HAART), requiring concomitant administration of three to four different agents, often with a high potential for drug-drug interactions (DDIs). This study aimed to determine the prevalence of possible DDIs between antiretrovirals (ARVs) themselves and other drugs. Design. Retrospective drug-utilisation study using data from from a national medicine claims database for the period 1 January to 31 December 2004. Setting. A section of the private healthcare sector in South Africa. Subjects. All ARV prescriptions (N=43482) claimed during 2004. The possible DDIs found were classified according to a clinical significant rating as described by Tatro7 (2005) in his book, “Drug Interactions – Facts and comparisons.” Results. A total of 5305882 medicine items were prescribed, of these, 1.92% (N=101 938) accounted for ARVs. Of the total number of 2595254 prescriptions, 1.68% (N=43 482), were ARVs. A total number of 18035 DDIs (81 different types) were identified, of these, 83.89%, (n=15130) were DDIs between ARVs and other drugs, while 16.11% (n=2905) were DDIs between ARVs themselves. Possible DDIs with a clinical significance level of 1 (major, n=17) and 2 (moderate, n=1436) represented 8.06% (n=1 453) of the total number of identified interactions. Conclusions. Since concomitant use of ARVs and other drugs used to treat HIV complications is increasing, there is a great need of understanding and anticipating these DDIs, overcoming them by dose adjustments and patient education by pharmacists, so that they are not life threatening to HIV/AIDS patients

Nutrient sensing modulates malaria parasite virulence

The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host, primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signalling networks that enable cells to sense and adapt to varying environmental conditions. Canonical nutrient-sensing pathways are presumed to be absent from the causative agent of malaria, Plasmodium, thus raising the question of whether these parasites can sense and cope with fluctuations in host nutrient levels. Here we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through rearrangement of their transcriptome accompanied by substantial adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology with SNF1/AMPKα, and yeast complementation studies suggest that it is part of a functionally conserved cellular energy-sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical for modulating parasite replication and virulence

Evolution of the TOR Pathway

The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and provide a practical framework on which experimental evidence can be compared between species. Here we performed phylogenetic analyses on the components of the TOR pathway and determined their point of invention. We find that the two TOR complexes and a large part of the TOR pathway originated before the Last Eukaryotic Common Ancestor and form a core to which new inputs have been added during animal evolution. In addition, we provide insight into how duplications and sub-functionalization of the S6K, RSK, SGK and PKB kinases shaped the complexity of the TOR pathway. In yeast we identify novel AGC kinases that are orthologous to the S6 kinase. These results demonstrate how a vital signaling pathway can be both highly conserved and flexible in eukaryotes

Dissociable hormonal responses to symptoms and stress in anorexia and bulimia nervosa

Background: Anorexia nervosa (AN) and bulimia nervosa (BN) are complex psychiatric conditions, in which both psychological and metabolic factors have been implicated. Critically, the experience of stress can precipitate loss-of-control eating in both conditions, suggesting an interplay between mental state and metabolic signaling. However, associations between psychological states, symptoms and metabolic processes in AN and BN have not been examined. Methods: Eighty-five women (n=22 AN binge/purge subtype, n=33 BN, n=30 controls) underwent remote salivary cortisol sampling and a two-day, inpatient study session to examine the effect of stress on cortisol, gut hormones (acyl-ghrelin, PYY, GLP-1) and food consumption. Participants were randomized to either an acute stress induction or control task on each day, and plasma hormones were serially measured before a naturalistic, ad libitum meal.Results: Cortisol awakening response (CAR) was augmented in AN but not BN relative to controls, with body mass index explaining the most variance in CAR (36%). Acute stress increased acyl-ghrelin and PYY in AN compared to controls; however, stress did not alter gut hormone profiles in BN. Instead, a group-by-stress interaction showed nominally reduced cortisol reactivity in BN, but not AN, compared to controls. Ad libitum consumption was lower in both patient groups and unaffected by stress.Conclusions: Findings extend previous reports of metabolic dysfunction in binge-eating disorders, identifying unique associations across disorders and under stress. Moreover, we observed disrupted homeostatic signaling in AN following psychological stress, which may explain, in part, the maintenance of dysregulated eating in this serious illness.</p

Methylphenidate use among students living in junior on-campus residences of the University of the Free State

Background: The use of methylphenidate as cognitive enhancer is a growing trend among students at tertiary institutions globally. This study aimed to determine the prevalence of methylphenidate use and co-use with alcohol among on-campus residence students of the University of the Free State (UFS). Methods: For this cross-sectional study, 10 junior residences were randomly selected and 1 761 anonymous questionnaires handed out for all students living in these residences during 2015. Data were collected on demographics, use of methylphenidate and co-use of methylphenidate with alcohol. Results: In total, 585 questionnaires (response rate 33.2%) were received and analysed. Sixty-six (11.3%) participants reported past-year use of methylphenidate. While only 18 (27.3%) of past-year users were diagnosed with ADHD, 44 (66.7%) obtained their supply through doctors’ prescriptions, 21 (31.8%) from friends without payment, and 4 (6.1%) bought it from illegal sources. Of the past-year users, 24.2% had used methylphenidate before consuming alcohol. Conclusion: Off-label prescribing, diversion of prescriptions and illegal trade in methylphenidate occur among students at the UFS. The frequent co-use of methylphenidate and alcohol may indicate a lack of information on the effects of the medication, rather than deliberate misuse. (Full text of the research articles are available online at www.medpharm.tandfonline.com/ojfp) S Afr Fam Pract 2017; DOI: 10.1080/20786190.2017.129269

Determination of an optimal dose of medetomidine-ketamine-buprenorphine for anaesthesia in the cape ground squirrel (Xerus inauris)

The optimal dose of medetomidine-ketamine-buprenorphine was determined in 25 Cape ground squirrels (Xerus inauris) undergoing surgical implantation of a temperature logger into the abdominal cavity. At the end of anaesthesia, the squirrels were given atipamezole intramuscularly to reverse the effects of medetomidine. The mean dose of medetomidine was 67.6±9.2 µg/kg, ketamine 13.6±1.9 mg/kg and buprenorphine 0.5±0.06 µg/kg. Induction time was 3.1 ± 1.4 min. This produced surgical anaesthesia for 21± 4.2 min. Atipamezole 232±92 µg/kg produced a rapid recovery. Squirrels were sternally recumbent in 3.5 ± 2.2 min

A stable ruthenium catalyst for productive olefin metathesis

New ruthenium carbene complexes 5 and 6, containing a rigid bicyclic phosphine moiety, have been prepared, and the structure of 5 has been unambiguously established by single-crystal X-ray diffraction studies. These ruthenium-based complexes show excellent stability to air and moisture, can be recycled by chromatography, and are available from simple precursors. They are efficient catalysts for various metathesis reactions, particularly for applications where high selectivity is required.</p