Pharmacokinetics of teicoplanin in patients undergoing chronic haemodialysis

In order to define a dose regimen of teicoplanin for patients undergoing chronic haemodialysis so that they achieved trough drug serum levels above 10 mg/l, two single doses of 5 and 10 mg/kg were administered intravenously in seven anuric patients immediately after the end of haemodialysis. Concentrations of teicoplanin were determined by a microbiological assay in samples collected from peripheral veins via the arterial and the venous lines of the fistulae and from the dialysate during haemodialysis. The administration of a 5 and 10 mg/kg dose gave mean C(max) of 62.80 and 122.43 mg/l, mean AUC of 526.43 and 1103.98 mg h/l, mean half life (t(1/2)) of 109.09 and 107.06 h, mean clearance rates of 12.85 and 12.44 ml/min, mean apparent volumes of distribution of 1.68 and 1.68 l/kg and mean volumes of distribution at steady state of 0.31 and 0.28 l/kg, respectively. Trough serum levels above 10 mg/l were found for 24 h after the administration of the 5 mg/kg dose and for 48 h after the administration of the 10 mg/kg dose. Teicoplanin was not detected in the dialysate. Its concentrations in both the arterial and the venous lines of the fistulae were similar. Based on the time period after the administration of teicoplanin where the desired trough serum levels were found and on the observed t(1/2), it is proposed that teicoplanin should be administered at a dose of 10 mg/kg at 48-72 h intervals, in patients undergoing chronic haemodialysis for the therapy of infections caused by Gram-positive cocci.     

Deoxyuridine accumulation in urine in thymidine phosphorylase deficiency (MNGIE)

We report the presence of the unusual nucleoside deoxyuridine in the urine of a patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) (MIM 603041) due to thymidine phosphorylase (TP:EC 2.4.2.4) deficiency. Thymidine, uracil and thymine were also elevated. We propose that inhibition of thymidylate synthetase by TMP leads to the accumulation of dUMP which may be degraded to deoxyuridine or metabolised to dUTP. Incorporation of dUTP into mtDNA may explain the multiple deletions characteristic of TP deficiency.     

A study on the effects of seasonal solar radiation on exposed populations

In the present study the effects of seasonal solar radiation (summer and winter) on exposed populations of two different age groups (20-25 and 40-55 years old) were investigated. In addition, the effects of external factors, such as hydrogen peroxide (H(2)O(2)) and gamma-irradiation, as well as the repair efficiency of human lymphocytes from these populations, was also evaluated. Our results show that the amount of DNA damage appears to be influenced by the exposure to solar radiation, with the summer exposure being the most damaging. Age was also found to be a significant factor, with the older population being more susceptible to solar radiation than the younger one. Season does not appear to affect the sensitivity to external DNA-damaging agents, while age does. Age was also found to have an effect on the DNA repair capacity of the examined populations.     

The effect of pre-operative anxiety on induction of anaesthesia with propofol

In this prospective study, we investigated the effects of anxiety on the induction dose of propofol and subsequent cardiovascular changes in 197 patients. Pre-operative state and trait anxiety scores were measured using the State Trait Anxiety Inventory. Propofol was administered at 40 mg x kg(-1) x h(-1). Propofol dose was recorded at loss of verbal response and when EEG Bispectral Index decreased to 50. Thereafter, propofol infusion rate was reduced to 8 mg x kg(-1) x h(-1). Cardiovascular data were collected for 15 min after starting induction. Maximum percentage decreases in heart rate and mean arterial pressure, and the point at which the latter occurred, were recorded. On multivariate analysis, anxiety scores did not significantly affect propofol dose or cardiovascular end-points, although Bispectral Index at loss of verbal response decreased with increasing trait anxiety (p = 0.02). Anxiety, measured using State Trait Anxiety Inventory, does not appear independently to affect the induction characteristics of propofol.     

Acute kidney injury in two children caused by renal hypouricaemia type 2

BACKGROUND: Renal hypouricaemia is a heterogeneous inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and nephrolithiasis. Type 1 is caused by a loss-of-function mutation in the SLC22A12 gene (OMIM #220150), while type 2 is caused by defects in the SLC2A9 gene (OMIM #612076). CASE-DIAGNOSIS/TREATMENT: The cases of two children, a 12- and a 14-year-old boy with acute kidney injury (proband 1: urea 9.4 mmol/l, creatinine 226 μmol/l; proband 2: urea 11.7 mmol/l, creatinine 202 μmol/l) are described. Both are offspring of nonconsanguineous couples in the UK. The concentrations of serum uric acid were consistently below the normal range (0.03 and 0.04 mmol/l) and expressed as an increase in the fractional excretion of uric acid (46 and 93 %). CONCLUSIONS: A sequencing analysis of the coding region of uric acid transporters SLC22A12 and SLC2A9 was performed. Analysis of genomic DNA revealed two unpublished missense transitions, p.G216R and p.N333S in the SLC2A9 gene. No sequence variants in SLC22A12 were found. Our findings suggest that homozygous and/or compound heterozygous loss-of-function mutations p.G216R and p.N333S cause renal hypouricaemia via loss of uric acid absorption and do lead to acute kidney injury.     

Platelet Activating Factor in Heart Failure: Potential Role in Disease Progression and Novel Target for Therapy

Heart failure (HF) is a complex syndrome with cardiac, renal, neurohormonal and sympathetic nervous system’s manifestations, the pathogenesis of which among others is connected to inflammation. PAF has local and systemic effects pertaining to HF progression since it causes a negative inotropic effect, it induces arrhythmias, it induces apoptosis and it is involved in inflammation and atherosclerosis. In the present review the role of PAF in HF will be thoroughly presented along with the relevant data on PAF enzymes and the potential role of PAF metabolic circuit as a novel pharmacological target.