The effects of hyponatraemia and subarachnoid haemorrhage on the cerebral vasomotor responses of the rabbit

Impairment of cerebral autoregulation and development of hyponatraemia are both implicated in the pathogenesis of delayed cerebral ischaemia and infarction following subarachnoid haemorrhage (SAH) but the pathophysiology and interactions involved are not fully understood. We have studied the effects of hyponatraemia and SAH on the cerebral vasomotor responses of the rabbit. Cerebrovascular reactivity to hypercapnia and cerebral autoregulation to trimetaphan-induced hypotension were determined in normal and hyponatraemic rabbits before and 6 days after experimental SAH produced by two intracisternal injections of autologous blood. Hyponatraemia (mean plasma sodium of 119 mM) was induced gradually over 48 h by administration of Desmopressin and intraperitoneal 5% dextrose. Sham animals received normal saline. The cerebrovascular reactivity (% change +/- SD in cortical CBF/mm Hg PaCO2, measured by hydrogen clearance) of hyponatraemic (4.8 +/- 3.0%) and SAH (1.3 +/- 2.0%) animals was significantly less (p less than 0.05) than control (11.6 +/- 4.0%) and sham (8 +/- 2.0%) animals, whereas the reactivity of hyponatraemic-SAH animals was preserved (9.8 +/- 6.0%). Hyponatraemia and SAH alone each significantly impaired CBF autoregulation but their combined effects were not additive. Systemic hyponatraemia impairs normal cerebral vasomotor responses but does not augment the effects of experimental SAH in the rabbit.     

Estrogen increases adrenergic- but not cholinergic-mediated production of inositol phosphates in rabbit uterus

alpha 1-Adrenergic and muscarinic cholinergic stimuli activate uterine contraction. Estrogen increases adrenergic but not cholinergic sensitivity of rabbit myometrium independent of its effects on adrenoceptor concentration. Since both alpha 1-adrenergic and muscarinic receptors are coupled to phosphatidylinositol hydrolysis, we tested the hypothesis that estrogen increases adrenergic- but not cholinergic-mediated inositol triphosphate production. We found that maximal production of inositol phosphates stimulated by norepinephrine was increased approximately 3-fold following estrogen treatment. Cholinergic-stimulated production was not increased by estrogen treatment. These results demonstrate that the effect of estrogen to enhance uterine adrenergic sensitivity is associated with an increased post-receptor response. The nature of the selectivity of estrogen for adrenergic versus cholinergic response remains obscure, but the results suggest the presence of parallel pathways for receptor activation of a common post-receptor response.     

On the Edge: a drama‐based mental health education programme on early psychosis for schools

Aims: On the Edge is a mental health education programme designed to support early intervention by increasing knowledge and understanding of early psychosis, reducing the stigma associated with mental health issues and improving awareness of avenues of help. The target audience was young people aged 14–22 years in schools and colleges. Methods: An interactive drama programme was developed through collaborative working across psychiatry, applied drama and those with direct experience of psychosis. A national tour engaged 2500 students in 71 performances that took place in 51 schools and colleges. The programme was evaluated against its aims with data collected both during and after the tour. Results: Quantitative and qualitative evaluation found significant gains with respect to all three aims. Thirty‐one schools developed supportive links with local mental health services. Conclusions: This programme shows the value and effectiveness of delivering health education on early psychosis through the medium of applied drama, and offers a model for a programme that can be incorporated into early intervention services. Lessons learned through delivering this programme are a valuable contribution towards future developments of mental health education programmes for schools.     

Preferential liver gene expression with polypropylenimine dendrimers.

Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration.     

Transvenous catheter–based microwave ablation for atrial flutter

We report a case of successful transvenous, catheter-based, cavotricuspid isthmus ablation for treatment of atrial flutter using microwave energy. Microwave energy was delivered at 900–930 MHz using 21 W of power. Bidirectional cavotricuspid isthmus conduction block was achieved by microwave ablation without any patient discomfort or complication during the procedure. Our initial experience suggests that transcatheter microwave ablation is feasible for the cure of typical atrial flutter.     

The antinociceptive effects of anterior pretectal stimulation in tests using thermal, mechanical and chemical noxious stimuli

Four behavioural tests have been used to study the antinociceptive effects of electrical stimulation of the anterior pretectal nucleus (APtN) in the rat. The antinociceptive effects of stimulating this nucleus, which lies dorsally in the posterior diencephalon, have recently been studied extensively but always using briefly applied heat stimuli. It is reported here that APtN stimulation effectively inhibited responses to briefly applied noxious pressure and longer-lasting noxious chemical (formalin) stimuli. Although the tail-flick reflex to noxious heat was very potently depressed by APtN stimulation, responses to noxious heat in the hot-plate test were not. Three doses of morphine were also studied with each test and it was concluded that 15 sec of 35 microA r.m.s. current into the APtN was as effective as 3-5 mg/kg morphine s.c. in the rat.