Mechanisms of Parkinson's Disease: Lessons from Drosophila.

The power of Drosophila genetics has attracted attention in tackling important biomedical challenges such as the understanding and prevention of neurodegenerative diseases. Parkinson's disease (PD) is the most common neurodegenerative movement disorder which results from the relentless degeneration of midbrain dopaminergic neurons. Over the past two decades tremendous advances have been made in identifying genes responsible for inherited forms of PD. The ease of genetic manipulation in Drosophila has spurred the development of numerous models of PD, including expression of human genes carrying pathogenic mutations or the targeted mutation of conserved orthologs. The genetic and cellular analysis of these models is beginning to reveal fundamental insights into the pathogenic mechanisms. Numerous pathways and processes are disrupted in these models but some common themes are emerging. These often implicate aberrant synaptic function, protein aggregation, autophagy, oxidative stress, and mitochondrial dysfunction. Moreover, an impressive list of small molecule compounds have been identified as effective in reversing pathogenic phenotypes, paving the way to explore these for therapeutic interventions.

The variability of goniometric measurements in ambulatory children with spastic cerebral palsy.

This study assessed the variability of six goniometric measurements commonly used in the assessment of children with cerebral palsy (CP). Three experienced paediatric physiotherapists recorded three consecutive measurements of six joint ranges from 12 children with spastic CP. A fourth measurement was recorded 1 week later. The order of measurement with regards to both joint measurement and tester, was randomised to ensure a balanced experimental design. A blinded procedure was adopted with masked goniometers and a second assessor present to record the measurement. Results, analysed using generalizability theory, showed same day and different day measurement error of +/-10-14 degrees (95% confidence limits) for the foot/thigh angle, abduction and internal rotation of the hip. The source of this was child-assessor and residual error. For ankle dorsiflexion and the popliteal angles, same day measurement error was similar. However, for joint ranges recorded on different days, error ranged from +/-18-28 degrees. The major source of this was systematic differences in measurements recorded on different days. Results show a need for caution when using goniometric measurements in clinical decision making, particularly in the more tone dependent biarticular muscles after an initial assessment.

A comparative study of five laboratory tests for foeto-placental dysfunction in late pregnancy.

Five foeto-placental function tests were studied in parallel in normal and abnormal late pregnancies with a view to establishing which test or tests is most satisfactorily able to identify the mother whose foetus is in danger.A critical examination of the levels in blood serum of two enzymes, placental phosphatase isoenzyme and cystine aminopeptidase, the polypeptide hormone placental lactogen (chorionic somatomammotrophin), and the oestrogen oestriol-17beta is described.A correlation was attempted beween clinical data and the results of the above laboratory analyses and also with the daily urine oestrogen output. The plasma and urine oestriol levels proved generally to be the more useful warning tests in late pregnancy, whilst the plasma cystine aminopeptidase was the least sensitive indicator of foeto-placental dysfunction.

Metabolism of penicillins to penicilloic acids and 6-aminopenicillanic acid in man and its significance in assessing penicillin absorption.

Penicillins can be metabolized to penicilloic acids in man, the extent being dependent on the penicillin structure. In the phenoxy penicillin series, phenoxymethyl penicillin was found to be particularly unstable, but the higher homologues were more stable. In the isoxazolyl series, oxacillin was unstable, and progressive insertion of halogen in the phenyl ring increased stability. Ampicillin and amoxycillin showed some instability, ampicillin possibly being the more stable. After intramuscular administration, carbenicillin was very stable in the body, ampicillin was fairly stable, and benzyl penicillin was unstable. It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin. Increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum. Penicilloic acids seemed to be more slowly cleared from the body than penicillins. The liver is probably the site of inactivation.