Ellagic acid, pomegranate and prostate cancer - a mini review.

There is currently a shifting focus towards finding natural compounds that may prevent or treat cancer, due to the problems that exist with current chemotherapeutic regimens. The fruit of the Punica granatum (pomegranate) contains hundreds of phytochemicals and pomegranate extracts have recently been shown to exhibit antioxidant properties, thought to be due to the action of ellagic acid, the main polyphenol in pomegranate. In this mini review the effects of pomegranate extracts and ellagic acid on the proliferation of prostate cancer cells and their future potential are discussed.

Inflammation and Anti-inflammatory strategies for alzheimer disease a mini review

Until recently, the central nervous system (CNS) has been thought to be an immune privileged organ. However, it is now understood that neuroinflammation is linked with the development of several CNS diseases including late-onset Alzheimer's disease (LOAD). The development of inflammation is a complex process involving a wide array of molecular interactions which in the CNS remains to be further characterized. The development of neuroinflammation may represent an important link between the early stages of LOAD and its pathological outcome. It is proposed that risks for LOAD, which include genetic, biological and environmental factors can each contribute to impairment of normal CNS regulation and function. The links between risk factors and the development of neuroinflammation are numerous and involve many complex interactions which contribute to vascular compromise, oxidative stress and ultimately neuroinflammation. Once this cascade of events is initiated, the process of neuroinflammation can become overactivated resulting in further cellular damage and loss of neuronal function. Additionally, neuroinflammation has been associated with the formation of amyloid plaques and neurofibrillary tangles, the pathological hallmarks of LOAD. Increased levels of inflammatory markers have been correlated with an advanced cognitive impairment. Based on this knowledge, new therapies aimed at limiting onset of neuroinflammation could arrest or even reverse the development of the disease.

Depression associates with Mini Nutritional Assessment (MNA), Vitamin B12 and Folate status::Findings from Belfast Elderly Longitudinal Free-Living Ageing STudy (BELFAST)

Introduction: An association between depression and folate has been found in clinical studies. Depression and dementia can contribute to nutritional deficiency. This study clinical depression in in octo/nonagenarians from the BELFAST study.
Method: In the BELFAST study, 38 free-living octo/nonagenarians (mean age 82 years), who apparently well and cognitively intact were followed up at 5 years and assessed using the Geriatric Depression Scale (GDS), Folstein (30 point), Mini Nutritional Assessment Tool (MNA) together with serum folate and vitamin B12 levels.
Results: Mean GDS was 3.4 (SD 2.5), serum folate 7.1 umol/l (SD 5.3) and B12 553 umol/l (458). With mean MNA and Folstein -25.8 (SD 2.7) and 27.6 (SD 2.7) respectively with no sex difference (p = 0.78; p = 0.36). 25% of subjects showed a GDS >5 indicating risk of mild depression and 21% had compromised nutritional status. MNA associated with GDS in male (r2 = 0.56 p = 0.01), but not in female elderly subjects (r2 = 0.01; p = 0.44). GDS score and lower serum folate were associated (r2 = -0.23; p = 0.01).
Conclusion: Overall there was the suggestion that nutritional status and depression might be linked in male subjects at 5 year follow-up in octo/nonagenarians from the BEFLAST study. The lower folate in subjects categorised at risk of mild depression might suggest vitamin supplementation could be useful.

A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease

OBJECTIVES: The behavioral and psychological symptoms of Alzheimer's disease (AD) are associated with significant patient and caregiver distress and increased likelihood of institutionalization. We attempted to characterize in detail these symptoms and the distress they cause to caregivers. METHODS: Patients with probable AD were assessed with the Mini-Mental State Exam (MMSE), Functional Assessment Staging (FAST), and the Neuropsychiatric Inventory With Caregiver Distress (NPI-D). RESULTS: Four hundred and thirty-five patients were recruited. Neuropsychiatric symptoms of all types were highly prevalent. The most common and most persistent symptom was apathy (75%). Delusional symptoms were the least persistent. Depressive and apathetic symptoms were the earliest to appear, and hallucinations, elation/euphoria, and aberrant motor behavior were the latest symptoms to emerge. Hallucinations were significantly more common in severe dementia. Symptoms of irritability were most prevalent in early disease. Total Neuropsychiatric Symptom score was significantly correlated with MMSE and FAST score. Caregivers rated their own emotional distress levels as moderate or severe for 10 out of 12 symptom domains. The sum total of caregiver distress was strongly correlated with total NPI-D but not cognition or functional state. Distress levels did not vary when analyzed according to the patients' place of residence. CONCLUSIONS: Potentially treatable neuropsychiatric symptoms are common in AD and represent a major source of distress among caregivers. The extent of neuropsychiatric symptomatology is seen to correlate with the level of functional and cognitive disability although some symptoms are variably persistent and related to disease stage.

The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease

BACKGROUND: Hypertension and cognitive impairment are prevalent in older people. It is known that hypertension is a direct risk factor for vascular dementia and recent studies have suggested hypertension also impacts upon prevalence of Alzheimer's disease. The question is therefore whether treatment of hypertension lowers the rate of cognitive decline. OBJECTIVES: To assess the effects of blood pressure lowering treatments for the prevention of dementia and cognitive decline in patients with hypertension but no history of cerebrovascular disease. SEARCH STRATEGY: The trials were identified through a search of CDCIG's Specialised Register, CENTRAL, MEDLINE, EMBASE, PsycINFO and CINAHL on 27 April 2005. SELECTION CRITERIA: Randomized, double-blind, placebo controlled trials in which pharmacological or non-pharmacological interventions to lower blood pressure were given for at least six months. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and extracted data. The following outcomes were assessed: incidence of dementia, cognitive change from baseline, blood pressure level, incidence and severity of side effects and quality of life. MAIN RESULTS: Three trials including 12,091 hypertensive subjects were identified. Average age was 72.8 years. Participants were recruited from industrialised countries. Mean blood pressure at entry across the studies was 170/84 mmHg. All trials instituted a stepped care approach to hypertension treatment, starting with a calcium-channel blocker, a diuretic or an angiotensin receptor blocker. The combined result of the three trials reporting incidence of dementia indicated no significant difference between treatment and placebo (Odds Ratio (OR) = 0.89, 95% CI 0.69, 1.16). Blood pressure reduction resulted in a 11% relative risk reduction of dementia in patients with no prior cerebrovascular disease but this effect was not statistically significant (p = 0.38) and there was considerable heterogeneity between the trials. The combined results from the two trials reporting change in Mini Mental State Examination (MMSE) did not indicate a benefit from treatment (Weighted Mean Difference (WMD) = 0.10, 95% CI -0.03, 0.23). Both systolic and diastolic blood pressure levels were reduced significantly in the two trials assessing this outcome (WMD = -7.53, 95% CI -8.28, -6.77 for systolic blood pressure, WMD = -3.87, 95% CI -4.25, -3.50 for diastolic blood pressure).Two trials reported adverse effects requiring discontinuation of treatment and the combined results indicated a significant benefit from placebo (OR = 1.18, 95% CI 1.06, 1.30). When analysed separately, however, more patients on placebo in SCOPE were likely to discontinue treatment due to side effects; the converse was true in SHEP 1991. Quality of life data could not be analysed in the three studies. There was difficulty with the control group in this review as many of the control subjects received antihypertensive treatment because their blood pressures exceeded pre-set values. In most cases the study became a comparison between the study drug against a usual antihypertensive regimen. AUTHORS' CONCLUSIONS: There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease. There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients given active treatment. This introduced bias. More robust results may be obtained by analysing one year data to reduce differential drop-out or by conducting a meta-analysis using individual patient data.

A 6-month open-label study of the effectiveness and tolerability of galantamine in patients with Alzheimer's disease

The objective of this study was to assess the effectiveness and tolerability of galantamine in patients with mild-to-moderate Alzheimer's disease (AD) in everyday clinical practice. Patient selection was made on 36 sequential patients attending Belfast City Hospital Memory Clinic between December 2000 and June 2001. Patients were treated with galantamine for 6 months, starting from 4 mg twice daily increasing to 8 mg twice daily and then to 12 mg twice daily at 4-weekly intervals. Patients (25 females, 11 males), mean age 78 years (59-90), were diagnosed with probable AD and had a mini-mental state examination (MMSE) score of 10-26. Efficacy was assessed using the MMSE, neuropsychiatric inventory (NPI), neuropsychiatric inventory caregiver distress (NPI-D) scale and the Bristol activities of daily living (B-ADL) scale at baseline and after 3 and 6 months of treatment. Mean improvements were noted on all four measures of efficacy at 3 and 6 months; improvements were significant on the MMSE, NPI and NPI-D at 3 months and on the NPI-D at 6 months. Galantamine was overall well tolerated. The most common adverse events were gastrointestinal, particularly nausea. Four patients stopped treatment due to adverse events, and seven were stabilised on 8 mg twice daily as they were unable to tolerate the target dose. This naturalistic study confirms clinical trial data, which shows galantamine improves cognition and behavioural symptoms and is overall well tolerated. © 2004 Blackwell Publishing Ltd.

Genetically increased risk of sleep disruption in alzheimer's disease

STUDY OBJECTIVES: To investigate the role of a monoamine A oxidase promoter polymorphism in sleep disruption in Alzheimer's disease (AD). DESIGN: A case-control association analysis. SETTING: Sleep disturbance in AD is common, is extremely stressful for caregivers, and increases the risk of institutionalisation. It remains unclear why only some patients develop sleep disturbance; neuropathologic changes of AD are not typically seen in the areas of the brain responsible for sleep. We hypothesized that the risk of sleep disturbance is, at least in part, influenced by the availability of serotonin used for melatonin synthesis secondary to polymorphic variation at the enzyme monoamine oxidase A (MAO-A). PATIENTS: Patients with AD diagnosed according to standard criteria. INTERVENTIONS: Data were collected using the Sleep domain of the Neuropsychiatric Inventory with Caregiver Distress. Patients' cognition and function were assessed using the Mini-Mental State Examination and the Functional Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp variable number tandem repeat of the MAO-A promoter was by standard methods. MEASUREMENTS AND RESULTS: Of 426 patients surveyed, 54% experienced sleep disturbance. We found that the high-activity 4-repeat allele of the MAO-A VNTR promoter polymorphism confers increased susceptibility to sleep disturbance (p = .008). A quantitative sleep disturbance score was significantly higher in the patients possessing MAO-A 4-repeat allele genotypes. APOE had no influence on the development of an altered sleep phenotype. CONCLUSIONS: We conclude that sleep disturbance in AD is common and distressing and is associated with genetic variation at MAO-A.

Statistical modelling of cement slurries for self compacting SIFCON containing silica fume

This paper reports a study carried out to develop a self-compacting fibre reinforced concrete containing a high fibre content with slurry infiltrated fibre concrete (SIFCON). The SIFCON was developed with 10% of steel fibres which are infiltrated by self-compacting cement slurry without any vibration. Traditionally, the infiltration of the slurry into the layer of fibres is carried out under intensive vibration. A two-level fractional factorial design was used to optimise the properties of cement-based slurries with four independent variables, such as dosage of silica fume, dosage of superplasticiser, sand content, and water/cement ratio (W/C). Rheometer, mini-slump test, Lombardi plate cohesion meter, J-fibre penetration test, and induced bleeding were used to assess the behaviour of fresh cement slurries. The compressive strengths at 7 and 28 days were also measured. The statistical models are valid for slurries made with W/C of 0.40 to 0.50, 50 to 100% of sand by mass of cement, 5 to 10% of silica fume by mass of cement, and SP dosage of 0.6 to 1.2% by mass of cement. This model makes it possible to evaluate the effect of individual variables on measured parameters of fresh cement slurries. The proposed models offered useful information to understand trade-offs between mix variables and compare the responses obtained from various test methods in order to optimise self-compacting SIFCON.

Factorial Design of Cement Slurries Containing Limestone Powder for Self-Consolidating Slurry-Infiltrated Fiber Concrete

Slurries with high penetrability for production of Self-consolidating Slurry Infiltrated Fiber Concrete (SIFCON) were investigated in this study. Factorial experimental design was adopted in this investigation to assess the combined effects of five independent variables on mini-slump test, plate cohesion meter, induced bleeding test, J-fiber penetration test and compressive strength at 7 and 28 days. The independent variables investigated were the proportions of limestone powder (LSP) and sand, the dosages of superplasticiser (SP) and viscosity agent (VA), and water-to-binder ratio (w/b). A two-level fractional factorial statistical method was used to model the influence of key parameters on properties affecting the behaviour of fresh cement slurry and compressive strength. The models are valid for mixes with 10 to 50% LSP as replacement of cement, 0.02 to 0.06% VA by mass of cement, 0.6 to 1.2% SP and 50 to 150% sand (% mass of binder) and 0.42 to 0.48 w/b. The influences of LSP, SP, VA, sand and W/B were characterised and analysed using polynomial regression which identifies the primary factors and their interactions on the measured properties. Mathematical polynomials were developed for mini-slump, plate cohesion meter, J-fiber penetration test, induced bleeding and compressive strength as functions of LSP, SP, VA, sand and w/b. The estimated results of mini-slump, induced bleeding test and compressive strength from the derived models are compared with results obtained from previously proposed models that were developed for cement paste. The proposed response models of the self-consolidating SIFCON offer useful information regarding the mix optimization to secure a highly penetration of slurry with low compressive strength

Influence of mix proprtions on rheolgy of cement grouts containing limestone powder

In this paper the parameters of cement grout affecting rheological behaviour and compressive strength are investigated. Factorial experimental design was adopted in this investigation to assess the combined effects of the following factors on fluidity, rheological properties, induced bleeding and compressive strength: water/binder ratio (W/B), dosage of superplasticiser (SP), dosage of viscosity agent (VA), and proportion of limestone powder as replacement of cement (LSP). Mini-slump test, Marsh cone, Lombardi plate cohesion meter, induced bleeding test, coaxial rotating cylinder viscometer were used to evaluate the rheology of the cement grout and the compressive strengths at 7 and 28 days were measured. A two-level fractional factorial statistical model was used to model the influence of key parameters on properties affecting the fluidity, the rheology and compressive strength. The models are valid for mixes with 0.35-0.42 W/B, 0.3-1.2% SP, 0.02-0.7% VA (percentage of binder) and 12-45% LSP as replacement of cement. The influences of W/B, SP, VA and LSP were characterised and analysed using polynomial regression which can identify the primary factors and their interactions on the measured properties. Mathematical polynomials were developed for mini-slump, plate cohesion meter, inducing bleeding, yield value, plastic viscosity and compressive strength as function of W/B, SP, VA and proportion of LSP. The statistical approach used highlighted the limestone powder effect and the dosage of SP and VA on the various rheological characteristics of cement grout