Determination of kanamycin plasma levels using LC-MS and its pharmacokinetics in patients with multidrug-resistant tuberculosis with and without HIV-infection

The objectives of the study were: (1) to determine kanamycin plasma concentrations using liquid chromatography coupled with mass spectrometry (LC-MS), (2) to investigate kanamycin pharmacokinetics (PK) in patients with multi-drug resistant tuberculosis (MDR-TB), (3) to find out whether HIV infection, kidney dysfunction and antiretroviral drugs influence kanamycin PK. The study was designed as a non-randomized study involving male and female HIV- positive and HIVnegative patients admitted for MDR-TB treatment. Blood samples were collected before (baseline) and ½, 1, 2, 4, 8 and 24 hours after intramuscular injection of kanamycin. LC-MS was used to quantify kanamycin plasma concentrations. Thirty one patients including 13 HIV (+) participated in the study. The lower limit of detection and lower limit of quantification of kanamycin were 0.06 μg/ml and 0.15 μg/ml respectively. Kanamycin PK parameters were described and there was no significant difference between HIV-positive and HIV-negative patients. A statistical significant difference (p=0.0126) was found in the renal function in HIV - positive and HIV - negative patients. However, this difference did not affect kanamycin elimination. No interactions have been identified between antiretroviral drugs and kanamycin. Conclusion: LC-MS analysis method is highly specific and highly sensitive in the detection and quantification of kanamycin plasma concentrations. Kanamycin PK in patients with MDR-TB was described. Due to a limited number of patients, we cannot rule out any influence of HIV - infection, renal impairment and antiretroviral drugs on kanamycin pharmacokinetics. The relationship between the area under the curve of kanamycin free plasma concentrations (fAUC) and its minimum inhibitory concentrations (MIC) on M.tuberculosis isolated from the sputum of each patient should be assessed. Therefore, kanamycin free plasma concentrations and MIC should be determined.Web of Scienc

Plasma non-esterified fatty acids in patients with multiple sclerosis

Objective: The purpose of this study was to investigate the levels of non-esterified fatty acids in plasma from patients with multiple sclerosis and further to correlate these findings with the neurological profile as measured by the Kurtzke Expanded Disability Status Scale. Methods: Plasma non-esterified fatty acids and esterified fatty acids from 30 control subjects and 31 patients with multiple sclerosis were measured by gas chromatography. Results: Non-esterified fatty acids C18:2n-6, C20:4n-6, C16:1n-7, C18:1n-7, C18:1n-9, C14:0, C16:0 and C18:0 were significantly increased in plasma from patients with multiple sclerosis, P ≤ 0.01, while esterified ed fatty acid C18:2n-6 was decreased, P = 0.003. Fatty acid PC C16:1n-7 and non-esterified fatty acids C16:1n-7, C18:1n-7 and C18:1n-9 showed positive and fatty acids C18:1n-9, C20:0, C22:0 and C24:0 showed inverse correlations with the Functional System Scores. Conclusions: We have identified increased monounsaturated non-esterified fatty acids in plasma from patients with multiple sclerosis as indicative of a worse disease outcome. Further, the decrease in fatty acid C18:2n-6, with increases in non-esterified fatty acids C18:2n-6 and C20:4n-6, suggested a role for these eicosanoid precursor fatty acids in the inflammatory condition experienced by these patients.University Research Fund of the Cape Peninsula University of Technology, South Africa

Association of the ENPP1 rs997509 polymorphism with obesity in South African mixed ancestry learners

Background: The Ectonucleotide Pyrophosphatase Phosphodiesterase1 (ENPP1) polymorphisms have been associated with metabolic traits. There is no data on the effect of ENPP1 in South African children or adults. Objective: To investigate the role of K121Q (rs1044498), rs997509 and rs9402349 in obesity and other components of the metabolic syndrome. Design: A case-control study. Subjects: Sixty four obese and 64 lean mixed ancestry learners. Setting: Western Cape, South Africa. Main outcome measure: The ENPP1 rs997509T allele is independently associated with obesity in children of mixed ancestry from South Africa. Results: The T allele frequency of the rs997509 differed significantly between obese and controls, p=0.0100 and increased the risk of being obese, p = 0.0238. Furthermore, the estimated effect of the T allele was an increase of 8.6 cm in waist circumference, 10.2 kg in weight and a corresponding 4.9 kg/m2 in BMI. Individuals carrying both the 121Q and the T allele of rs997509 were more associated with obesity (odds ratio = 3.85, 95% CI: 1.13 to 13.09) whilst those carrying the C allele of rs997509 in the presence of 121Q were likely to be lean with odds ratio of obesity 0.41 (95% CI: 0.19 to 0.87). Conclusion: Our findings suggest that ENPP1 polymorphisms may contribute to different metabolic characteristics, all of which are associated with insulin resistance in mixed ancestry children of South Africa. However, a larger study is required to confirm findings of this study