Endogenous vasopressin and baroreflex mechanisms

This article reviews the anatomical and functional evidence for ascending pathways from specific brain regions to the PVN and SON which could influence AVP release. The majority of evidence favours the main projection being from a region in the caudal VLM which may coincide with the noradrenergic neurons of the A₁ cell group. However, the transmitter(s) involved have yet to be identified, and whether the pathway is excitatory and/or inhibitory remains to be fully resolved.Anatomical and functional evidence is reviewed for descending projections from the SON and PVN to specific brain regions involved in cardiovascular control, and their possible involvement in baroreflex mechanisms is discussed. However, there is little unequivocal evidence that AVP is the main neurotransmitter utilized by descending projections from PVN to NTS and DMX. While, in some situations, circulating endogenous AVP exerts cardiovascular effects, details of its putative influences on baroreflex mechanisms are lacking.     

Neurological disorders and violence: a systematic review and meta-analysis with a focus on epilepsy and traumatic brain injury

The objectives of this study were to systematically review and meta-analyze the research literature on the association of common neurological disorders and violence. Keywords relating to neurological disorders and violence were searched between 1966 and August 2008. Case–control and cohort studies were selected. Odds ratios of violence risk in particular disorders compared with controls were combined using fixed-effects meta-analysis with the data presented in forest plots. Sensitivity analyses were conducted to identify possible differences in risk estimates across surveys. Information on risk factors for violence was extracted if replicated in more than one study. Nine studies were identified that compared the risk of violence in epilepsy or traumatic brain injury compared with unaffected controls. For the epilepsy studies, the overall pooled odds ratio for violent outcomes was 0.67 [95% confidence interval (CI) 0.46–0.96]. For traumatic brain injury, the odds ratio was 1.66 (95% CI 1.12–2.31). An additional 11 case–control studies investigated factors associated with violence in epilepsy and traumatic brain injury. It was not possible to meta-analyze these data. Comorbid psychopathology was associated with violence. Data on other neurological conditions was limited and unreplicated. In conclusion, although the evidence was limited and methodological quality varied, epilepsy and traumatic brain injury appeared to differ in their risk of violence compared with control populations. Longitudinal studies are required to replicate this review’s provisional findings that epilepsy is inversely associated with violence and that brain injury modestly increases the risk, and further research is needed to provide information on a broader range of risk factors.     

Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.     

Further evidence of preserved memory function in Alzheimer's disease

Memory performance of elderly patients in the early stages of Alzheimer's disease (DAT) was compared with that of elderly control subjects. In explicit tests of recognition memory, which involve conscious recollection, the DAT patients were grossly impaired. In implicit tests of anagram solution and wordstem completion, which do not require conscious recollection, the DAT patients were not impaired. These findings further support the idea that a separate memory system, episodic memory, underlies conscious recollection, that it is this system which is most commonly damaged in amnesia, and that memory systems not involving conscious recollection may be spared in the early stages of Alzheimer's disease.     

Evidence for two leukotriene receptor types in the guinea-pig isolated ileum

Leukotriene (LT) receptors in the guinea-pig ileum were characterized using LTB4, LTC4, LTD4 and LTE4 and the LT antagonists FPL 55712, ICI 198615 and (+/-)SKF 104353. LTB4 was inactive but the other LTs induced concentration-related contractions. LTC4 responses differed to those induced by LTD4 or LTE4. Inhibitors of LT metabolism had no significant effects on any LT responses. LTD4 contractions were inhibited by all three antagonists but a resistant response was apparent at concentrations of ICI 198615 greater than 10(-8) M. All three antagonists were weak/inactive against LTC4. LTE4 was a partial agonist which antagonized LTD4 responses but had little or no activity against LTC4 or histamine. These results suggest that two distinct LT receptor types exist on guinea-pig ileum. One type is predominantly activated by LTD4 and is antagonized by three structurally distinct LT antagonists and the partial agonist LTE4. The second type is predominantly activated by LTC4 and is insensitive to the LT antagonists.     

Effects of chronic infusions of alpha-trinositol on regional and cardiac haemodynamics in conscious rats.

1. Male, Long Evans rats (350-450 g) were chronically instrumented for the measurement of renal, mesenteric and hindquarters haemodynamics, and were given three consecutive, 24 h infusions of vehicle (sterile saline at 0.3 ml h-1, n = 8) or alpha-trinositol (D-myo-inositol-1,2,6-triphosphate) at 5, 20 and 80 mg kg-1 h-1 (0.3 ml h-1; n = 9). During infusion of alpha-trinositol at 5 or 20 mg kg-1 h-1, cardiovascular changes were little different from those seen during saline infusion. However, during infusion of alpha-trinositol at 80 mg kg-1 h-1 there were increases in hindquarters vascular conductance, renal flow and vascular conductance, that were all significantly different from the changes seen in the saline group. Infusion of alpha-trinositol at the high dose in naive rats (n = 8) had even more marked vasodilator effects. 2. Two groups of rats (n = 8 in each), chronically instrumented for the measurement of cardiac haemodynamics, were given 48 h infusions of saline (0.3 ml h-1) or alpha-trinositol (2 mg kg-1 bolus, 80 mg kg-1 h-1 infusion at 0.3 ml h-1). During the infusion of saline, there were slight reductions in heart rate, cardiac index, peak aortic flow, dF/dtmax and central venous pressure. In the animals receiving alpha-trinositol, with the exception of central venous pressure, all the above variables, together with total peripheral conductance, increased. 3. These results, collectively, indicate that incremental infusions of alpha-trinositol do not reveal its full vasodilator potential, possibly due to concurrent activation of counter-regulatory vasoconstrictor mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early gastric cancer: a report of 30 cases

Thirty patients with early gastric cancer have been reviewed. Endoscopy demonstrated gastric abnormality in 93% of patients examined and biopsy was accurate in 96% of cases. Twenty-nine patients were treated by partial gastrectomy, although three required further procedures. The commonest morphological type was type III (45%). Five patients with early gastric cancer had lymph node spread at the time of presentation. The relative 5-year survival rate was 68%. Four patients eventually died of gastric cancer. Three patients (10%) developed a second primary carcinoma. The significance of this diagnosis is emphasized and selective screening is considered.     

Recombinant α2(IV)NC1 domain of type IV collagen is an effective regulator of retinal capillary endothelial cell proliferation and inhibits pre-retinal neovascularisation

Background A recombinant form of the α2(IV)NC1 domain of type IV collagen has been shown to have potent anti-angiogenic activity although this peptide has not been studied in the context of proliferative retinopathies. In the current investigation we examined the potential for α2(IV)NC1 to regulate retinal microvascular endothelial cell function using a range of in vitro and in vivo assay systems. Materials and methods α2(IV)NC1 at concentrations between 0.1 and 1 μg/ml was added to retinal microvascular endothelial cells (RMECs) followed by assessment of cell attachment, proliferation and survival. This agent was also tested within a novel in vitro three-dimensional retinal angiogenesis assay and the number of angiogenic sprouts quantified. α2(IV)NC1 was also delivered intra-vitreally to mice with oxygen-induced proliferative retinopathy (OIR) and neovascularisation evaluated in comparison with vehicle-treated controls. Results RMECs treated with α2(IV)NC1 (0.1, 0.5 and 1 μg/ml) showed delayed attachment at 3 h post-seeding, although this deficit had been restored at the 6-h time point. BrdU assay of DNA replication revealed that confluent RMECs treated with α2(IV)NC1 showed no measurable response in comparison with vehicle-treated controls. By contrast, proliferation of sub-confluent RMECs was significantly reduced by α2(IV)NC1 at 0.5 μg/ml (P<0.01). α2(IV)NC1 also induced apoptosis in RMECs and inhibited angiogenesis of pre-existing retinal vascular networks in vitro (P<0.001). Intra-vitreal injection of α2(IV)NC1 in the OIR model significantly inhibited pre-retinal neovascularisation compared with vehicle-treated controls (P<0.001). Conclusion α2(IV)NC1 inhibits angiogenesis in the retinal microvasculature. This recombinant protein has potential for the treatment of neovascularisation in proliferative retinopathies. BioStratum Inc. did not sponsor this research in any way. None of the authors are paid consultants with this company.