How can health service users contribute to the NHS research and development programme?

The National Childbirth Trust, along with other groups of health service users, is working with health professionals and researchers in planning clinical trials, setting priorities for research, systematically reviewing research reports, and getting research findings into practice. User groups may bridge the gap between the public and researchers by explaining research issues to a wide audience, presenting the needs and views of health service users to the research community, and suggesting how members of the public may be approached for their views directly. Service users recognise their need for training and support, and they call for development and evaluation of this work.     

The oncolytic peptide LTX-315 triggers necrotic cell death

The oncolytic peptide LTX-315 has been designed for killing human cancer cells and turned out to stimulate anti-cancer immune responses when locally injected into tumors established in immunocompetent mice. Here, we investigated the question whether LTX-315 induces apoptosis or necrosis. Transmission electron microscopy or morphometric analysis of chromatin-stained tumor cells revealed that LTX-315 failed to induce apoptotic nuclear condensation and rather induced a necrotic phenotype. Accordingly, LTX-315 failed to stimulate the activation of caspase-3, and inhibition of caspases by means of Z-VAD-fmk was unable to reduce cell killing by LTX-315. In addition, 2 prominent inhibitors of regulated necrosis (necroptosis), namely, necrostatin-1 and cycosporin A, failed to reduce LTX-315-induced cell death. In conclusion, it appears that LTX-315 triggers unregulated necrosis, which may contribute to its pro-inflammatory and pro-immune effects.     

Cat heart acetylcholine: Unilateral vagotomy studies with pyrolysis-mass fragmentography

The distribution of acetylcholine (ACh) in the cat heart was investigated by pyrolysis-gas chromatography (PGC) and pyrolysis-mass fragmentography (PMF) techniques. The hearts were dissected into various regions and homogenized in the presence of butyrycholine (or propionylcholine) as internal standard. The choline esters were isolated and analyzed by PGC or by PMF (at m/e 58). A pattern of distribution for ACh was found to be the same as I have previously described (1,2). Some cats were subjected to either a right or a left unilateral cervical vagotomy 4 weeks before removal and analysis of heart tissue. Hearts from unilateral (right or left) vagotomized cats did not differ from controls in the ACh content of any heart area examined. These results are consistent with the idea that intact parasympathetic neurons may compensate for the denervation following unilateral vagotomy.     

Which drug for the adult epileptic patient: phenytoin or valproate?

A series of 140 previously untreated patients with tonic-clonic or partial seizures were randomised to receive either phenytoin or sodium valproate. There was no difference between the treatment groups in pretreatment variables that might influence outcome. Sodium valproate and phenytoin in the treatment of tonic-clonic or partial seizures showed no difference in efficacy as regards time to two year remission or time to first seizure. When the possible prognostic factors were studied, including history and results of clinical examination and investigations before treatment; the only factor which influenced the proportion of patients achieving two year remission was type of seizure. Patients with a clinical history of partial seizures did significantly less well than those with a history of tonic-clonic seizures only. This study showed no major difference in efficacy between sodium valproate and phenytoin in adults with recent onset of epilepsy, irrespective of the type of seizures that the patient suffered.     

Neuronal Basis of Innate Olfactory Attraction to Ethanol in Drosophila

The decision to move towards a mating partner or a food source is essential for life. The mechanisms underlying these behaviors are not well understood. Here, we investigated the role of octopamine – the invertebrate analogue of noradrenaline – in innate olfactory attraction to ethanol. We confirmed that preference is caused via an olfactory stimulus by dissecting the function of the olfactory co-receptor Orco (formally known as OR83b). Orco function is not required for ethanol recognition per se, however it plays a role in context dependent recognition of ethanol. Odor-evoked ethanol preference requires the function of Tbh (Tyramine β hydroxalyse), the rate-limiting enzyme of octopamine synthesis. In addition, neuronal activity in a subset of octopaminergic neurons is necessary for olfactory ethanol preference. Notably, a specific neuronal activation pattern of tyraminergic/octopaminergic neurons elicit preference and is therefore sufficient to induce preference. In contrast, dopamine dependent increase in locomotor activity is not sufficient for olfactory ethanol preference. Consistent with the role of noradrenaline in mammalian drug induced rewards, we provide evidence that in adult Drosophila the octopaminergic neurotransmitter functions as a reinforcer and that the molecular dissection of the innate attraction to ethanol uncovers the basic properties of a response selection system.     

Macrosatellite epigenetics: the two faces of DXZ4 and D4Z4

Almost half of the human genome consists of repetitive DNA. Understanding what role these elements have in setting up chromatin states that underlie gene and chromosome function in complex genomes is paramount. The function of some types of repetitive DNA is obvious by virtue of their location, such as the alphoid arrays that define active centromeres. However, there are many other types of repetitive DNA whose evolutionary origins and current roles in genome biology remain unknown. One type of repetitive DNA that falls into this class is the macrosatellites. The relevance of these sequences to disease is clearly demonstrated by the 4q macrosatellite (D4Z4), whereupon contraction in the size of the array is associated with the onset of facioscapulohumeral muscular dystrophy. Here, I describe recent findings relating to the chromatin organization of D4Z4 and that of the X-linked macrosatellite DXZ4, highlighting the fact that these enigmatic sequences share more than a similar name.