Therapeutic potential of cannabinoids in neurodegenerative disorders: a selective review.

The endocannabinoid system (ECS) is now recognised as an important modulator of various central nervous system processes. More recently, an increasing body of evidence has accumulated to suggest antioxidant, anti-inflammatory and neuroprotective roles of ECS. In this review we discuss the role and therapeutic potential of ECS in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, Huntington's disease, Tourette's syndrome, brain ischemia and amyotrophic lateral sclerosis (ALS).

Death-associated protein kinase (DAPK1) in cerebral cortex of late-onset Alzheimer's disease patients and aged controls.

Aims: Here our objective was to detect the pro-apoptotic serine/threonine kinase death-associated protein kinase (DAPK1) in aged human cerebral cortex and to test the hypothesis that DAPK1 abundance is associated with late-onset Alzheimer's disease (AD).

Methods: Using Western analysis and immunohistochemistry we evaluated post mortem frontal cerebral cortex from patients with severe AD (mean age 76 years, range 66-91, n = 11, all male), and from control cases without serious central nervous system illness (mean age 77 years, range 61-95, n = 12, all male). We also examined brains of Tg2576 transgenic mice (males, aged 16-21 months), a model for chronic amyloid-induced brain injury.

Attitudes of old age psychiatrists in England and Wales to the use of mood stabilizer drugs.

Objective: This study investigates attitudes to the prescription of mood stabilizer drugs for older patients by old age psychiatrists.

Methods: From a sample of 508 members of the Old Age Faculty of the Royal College of Psychiatrists practicing in England and Wales, 188 (37%) took part in a postal questionnaire survey. A proforma questionnaire investigating opinions about potential indications for, and current concerns about, mood stabilizer drugs was sent to all participants.

White matter lesions on magnetic resonance imaging and their relationship with vascular risk factors in memory clinic attenders.

Background: The association between white matter lesions on magnetic resonance imaging (MRI) and the presence of vascular risk factors has been investigated in different populations, and results have varied widely. However, this relationship has not been adequately addressed in memory clinic attenders who have relatively early cognitive impairment.

Objectives: This study was undertaken to determine the relationship between the severity of white matter lesions and vascular risk factors in elderly subjects referred to a Memory Clinic, irrespective of their diagnoses.

A comparison of the effects of Snoezelen and reminiscence therapy on the agitated behaviour of patients with dementia.

Background: Behavioural disturbance, such as agitation, is a common feature of dementia, and causes significant problems and distress for carers. Snoezelen is increasingly used with people who have dementia, but there is limited evidence of its efficacy.

Objective: This crossover randomised controlled study aimed to evaluate the effect of Snoezelen on the mood and behaviour of patients with dementia, in comparison to the effect of an established and accepted intervention, reminiscence therapy.

Extrapyramidal signs in cognitively intact elderly people.

Aim: to investigate the prevalence of extrapyramidal signs in elderly people and their relationship to disease.

Setting And Subjects: 151 non-demented subjects age 65 and over living within a defined geographical area in Nottingham who were participating in the MRC multicentre Cognitive Function and Ageing Study.

Measurements: subjects were assessed at home.

An investigation of visual hallucinosis and visual sensory status in dementia.

Introduction: Visual hallucinosis occurs frequently amongst patients with dementia and there is some evidence of an association between hallucinosis and impaired visual function. This study examined the association between objectively rated visual acuity, ambient illumination levels and hallucinosis in patients with dementia.

Methods: Thirty dementia patients with visual hallucinosis plus 30 non-hallucinating dementia patients were recruited from referrals to community mental health teams in Leicestershire.

A retrospective study of neuroradiological abnormalities detected on structural magnetic resonance imaging of the brain in elderly patients with cognitive impairment.

Background: The aim of the study was to investigate the relationship between neuroradiological and clinical diagnosis in patients presenting with cognitive impairment, and also the relationship between the neuroradiological abnormalities and cognitive function as assessed by the Mini-Mental State Examination (MMSE) score.

Methods: One hundred and four elderly subjects (65 years and over) with cognitive impairment, referred to secondary hospital services and who had brain magnetic resonance imaging (MRI) scans as part of routine clinical investigations, were studied by review of their MRI scans using a standardized procedure and by examination of the case notes.

Results: In patients with a clinical diagnosis of senile dementia Alzheimer-type (SDAT), the diagnosis was reviewed in 11.

Altered pupillary size and darkness and light reflexes in Alzheimer's disease.

The purpose was to compare resting pupil diameter in darkness and light, and the pupillary darkness and light reflexes between a group of patients with Alzheimer's disease and a group of healthy old people. Nine medication free patients with Alzheimer's disease and nine healthy control subjects, matched for sex and age with the patients, participated. There were six men and three women and the median age was 72 years in both groups.

Changes in autonomic function with age: a study of pupillary kinetics in healthy young and old people.

The object of the study was to compare resting pupil diameter in darkness and light, and the pupillary darkness and light reflexes between a group of young and elderly healthy subjects. Twelve young (eight men, four women; median age 19.5 years) and 14 elderly subjects (six men, eight women; median age 69 years) participated.

Dementia and 'borderline dementia' in Britain: 8-year incidence and post-screening outcomes.

Survivors from a nationally representative sample of elderly people originally screened in 1985 were reassessed in 1989 and again in 1993. On each occasion respondents were rated as cognitively impaired, borderline impaired or unimpaired (using a brief information/orientation scale), with the validity of these ratings assessed in subsequent clinical interviews. Where follow-up screening was not possible, information was derived from death certificates and hospital case-notes.

A three-month follow-up of psychological morbidity after early miscarriage.

The loss of a pregnancy in the first trimester is a common event and recent research has identified high levels of psychological distress amongst women who have miscarried. We believe this study is the first to examine the phenomenon from a longitudinal perspective using standardized measures. A sample of 65 women was rated for anxiety and depression using the Hospital Anxiety and Depression Scale at intervals of one, six and 12 weeks following early miscarriage.

Psychological aspects of miscarriage: attitudes of the primary health care team.

A questionnaire surveying the attitudes of general practitioners, health visitors, community midwives and district nurses towards the psychological aspects of miscarriage was distributed to a random sample of 50 staff in each professional group. The response rate was 78%. A large majority of all staff surveyed (76%) agreed that miscarriage is frequently associated with significant psychological distress and 90% agreed that women should be routinely encouraged to explore and discuss their feelings following such an event.

Protein kinase C and membrane transport: divergent responses of Na+/K+/Cl- cotransport and sugar transport to exogenous diacylglycerol.

Even though the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) is known to bind to and activate protein kinase C (PKC), it is still not certain that all cellular responses to phorbol esters are necessarily mediated by PKC. In BALB/c 3T3 preadipose cells, TPA has previously been shown to rapidly inhibit Na+K+Cl- -cotransport activity, stimulate 2-deoxyglucose uptake and induce ornithine decarboxylase activity. The cell-permeable diacylglycerol sn-1,2-dioctanoylglycerol (DiC8) was used in order to distinguish between PKC-dependent and -independent responses of BALB/c 3T3 cells.

A phorbol ester-nonproliferative variant of Swiss 3T3 cells is deficient in Na+K+Cl- cotransport activity.

The identity of the genetic defect(s) in Swiss 3T3 TNR-2 and TNR-9 that confers nonresponsiveness to the proliferative effect of 12-0-tetradecanoylphorbol-13-acetate (TPA) is not known. In BALB/c 3T3 cells, loss (via mutation) of a specific membrane ion transport system, the furosemide-sensitive Na+K+Cl- cotransporter, is associated with decreased responsiveness to TPA. In this study, the transport properties of parental Swiss 3T3 cells and the TPA-nonresponsive lines TNR-2 and TNR-9 were determined in the presence and absence of TPA.

Phorbol esters and mitogenesis: comparison of the proliferative response of parental and Na+K+Cl- -cotransport-defective BALB/c 3T3 cells to 12-0-tetradecanoylphorbol-13-acetate.

The ability of the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) to stimulate the growth of quiescent BALB/c 3T3 cell lines lacking Na+K+Cl- cotransport activity was tested. We have previously isolated and characterized two mutant cell lines defective in this important ion transport system by mutagenesis and selection in medium containing low K+. To test our hypothesis that loss of this transport activity might abrogate the proliferative response to TPA, two kinds of mitogenesis assays were performed.

Phorbol esters and gene expression: the role of rapid changes in K+ transport in the induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate in BALB/c 3T3 cells and a mutant cell line defective in Na+K+Cl- cotransport.

A BALB/c 3T3 preadipose cell line defective in Na+K+Cl- cotransport (3T3-E12a cells) has been used to study the relationship between phorbol ester-induced rapid changes in cation fluxes and changes in expression of a gene known to be modulated by this agent. In contrast to its effect on parental 3T3 cells, 12-O-tetradecanoylphorbol-13-acetate (TPA) did not inhibit either furosemide-sensitive 86Rb+ influx or the rate of 86Rb+ efflux from preloaded mutant cells. TPA-induced changes in intracellular K+ content were diminished in 3T3-E12a cells as compared with parental cells.