Neurogenic mechanisms in bladder and bowel ageing

The prevalence of both urinary and faecal incontinence, and also chronic constipation, increases with ageing and these conditions have a major impact on the quality of life of the elderly. Management of bladder and bowel dysfunction in the elderly is currently far from ideal and also carries a significant financial burden. Understanding how these changes occur is thus a major priority in biogerontology. The functions of the bladder and terminal bowel are regulated by complex neuronal networks. In particular neurons of the spinal cord and peripheral ganglia play a key role in regulating micturition and defaecation reflexes as well as promoting continence. In this review we discuss the evidence for ageing-induced neuronal dysfunction that might predispose to neurogenic forms of incontinence in the elderly

Helios is a key transcriptional regulator of outer hair cell maturation

The sensory cells that are responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with the OHCs being necessary for sound sensitivity and tuning1. Both cell types are thought to arise from common progenitors; however, our understanding of the factors that control the fate of IHCs and OHCs remains limited. Here we identify Ikzf2 (which encodes Helios) as an essential transcription factor in mice that is required for OHC functional maturation and hearing. Helios is expressed in postnatal mouse OHCs, and in the cello mouse model a point mutation in Ikzf2 causes early-onset sensorineural hearing loss. Ikzf2cello/cello OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of crucial OHC-expressed genes such as Slc26a5 (which encodes prestin) and Ocm. Moreover, we show that ectopic expression of Ikzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating that Ikzf2 can partially shift the IHC transcriptome towards an OHC-like identity

Speciation of inorganic selenium and selenoamino acids by an HPLC-UV-HG-AFS system

For the on-line speciation of selenocystine (SeCys), selenomethionine (SeMet), selenoethionine (SeEt), selenite (Se(IV)) and selenate (Se(VI)), a high-performance liquid chromatography-UV irradiation-hydride generation-atomic fluorescence spectro- metric method is described. Separation was carried out on a conventional reversed-phase C18 column modified with didodecyl- dimethylammonium bromide with gradient elution applying two concentrations of ammonium acetate as the mobile phase. UV irradiation and hydride generation parameters were optimized. The obtained detection limits for SeCys, SeMet, SeEt, Se(IV) and Se(VI) were 0.31, 0.43, 0.7, 0.44 and 0.32 ng ml(−)1, respectively, using a 100-wl loop. The method was tested with spiked mineral water and two volunteers' urine samples

Unlicensed and off label prescribing of drugs in general practice

AIM—To determine the incidence and nature of unlicensed and off label prescribing of drugs for children in general practice.
METHODS—A retrospective analysis of all prescriptions for one year involving children (aged 12 years or under) from a single suburban general practice in the English Midlands. Prescribed drugs were categorised as licensed, unlicensed (without a product licence), or used in an off label way (outside the terms of their product licence).
RESULTS—During 1997 there were 3347 prescription items involving 1175 children and 160 different drugs. A total of 2828 (84.5%) prescriptions were for licensed medicines used in a licensed way; 10 (0.3%) were for unlicensed medicines; and 351 (10.5%) were licensed medicines used in an off label way. For 158 (4.7%) the information was insufficient to determine licence status.
CONCLUSION—This is the first study to show that a significant number of drugs prescribed for children by general practitioners are off label and highlights the anomalies and inadequacies of drug information for prescribers.