Medical Research

Supercritical fluid extraction of ecdysterone from the roots of Achyranthes bidentata BL.

Ecdysterone has been found in a great many plants and animals and has some valuable pharmaceutical properties. The present study was conducted to investigate optimal conditions for the extraction of the compound by supercritical fluid extraction from the roots of Achyranthes bidentata BL. An orthogonal array design (OAD), OA(9)(3(4)), was employed as a chemometric method for optimization of the extraction of ecdysterone from the herbal medicine. Four parameters, namely, pressure and temperature of the supercritical fluid, the dynamic extraction time, and the flow rate of dimethyl sulfoxide, were studied and optimized by a three-level OAD. Determinations of the extracts were performed by high-performance liquid chromatography. The effects of the parameters were studied using analysis of variance. The results shown that the yield of ecdysterone could be influenced by the four parameters to a similar degree. The yield for DMSO-modified supercritical CO(2) was in the range from 0.65 to 1.03 mg/g under the selected conditions. In comparison with methanol-modified supercritical CO(2 )and Soxhlet extraction, a higher yield was obtained when DMSO-modified supercritical CO(2) was used.

J Sep Sci. 2008 Apr 3
Zheng Y, Liu B, Chen M, Chen T.
Department of Bioengineering and Pharmaceutics, Ningbo Institute of Technology, Zhejiang University, Ningbo, China. Fax: +86-574-88229516.

The efficiency of a vaccine largely depends on the appropriate targeting of the innate immune system, mainly through prolonged delivery of antigens and immunomodulatory substances to professional antigen-presenting cells in the lymphoid environment. Particulate antigens, such as virus-like particles (VLP) induce potent immune responses. However, little is known about the relative importance of direct drainage of free antigen to lymph nodes (LN) versus cellular transport and the impact of particle size on the process. Here, we show that nanoparticles traffic to the draining LN in a size-dependent manner. Whereas large particles (500-2000 nm) were mostly associated with dendritic cells (DC) from the injection site, small (20-200 nm) nanoparticles and VLP (30 nm) were also found in LN-resident DC and macrophages, suggesting free drainage of these particles to the LN. In vivo imaging studies in mice conditionally depleted of DC confirmed the capacity of small but not large particles to drain freely to the LN and demonstrated that DC are strictly required for transport of large particles from the injection site to the LN. These data provide evidence that particle size determines the mechanism of trafficking to the LN and show that only small nanoparticles can specifically target LN-resident cells.

.Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF.
Cytos Biotechnology, Schlieren, Switzerland.
Eur J Immunol. 2008 Apr 3

Assessing the validity and reliability of the Pool Activity Level (PAL) Checklist for use with older people with dementia

Activity is key to maintaining physical and mental health and well-being. However, as dementia affects the ability to engage in activity, care-givers can find it difficult to provide appropriate activities. The Pool Activity Level (PAL) Checklist guides the selection of appropriate, personally meaningful activities. The aim of this study was to assess the reliability and validity of the PAL Checklist when used with older people with dementia. A postal questionnaire sent to activity providers assessed content validity. Validity and reliability were measured in a sample of 60 older people with dementia. The questionnaire response rate was 83% (102/122). Most respondents felt no important items were missing. Seven of the nine activities were ranked as ‘very important’ or ‘essential’ by at least 77% of the sample, indicating very good content validity. Correlation with measures of cognition, severity of dementia and activity performance demonstrated strong concurrent validity. Inter-item correlation indicated strong construct validity. Cronbach’s alpha coefficient measured internal consistency as excellent (0.95). All items achieved acceptable test-retest reliability, and the majority demonstrated acceptable inter-rater reliability. We conclude that the PAL Checklist demonstrates adequate validity and reliability when used with older people with dementia and appears a useful tool for a variety of care settings.

Aging Ment Health. 2008 Mar;12(2):202-11.
.Wenborn J, Challis D, Pool J, Burgess J, Elliott N, Orrell M.
Department of Mental Health Sciences, University College London, UK.

Assessing the validity and reliability of the Pool Activity Level (PAL) Checklist for use with older people with dementia.

Activity is key to maintaining physical and mental health and well-being. However, as dementia affects the ability to engage in activity, care-givers can find it difficult to provide appropriate activities. The Pool Activity Level (PAL) Checklist guides the selection of appropriate, personally meaningful activities. The aim of this study was to assess the reliability and validity of the PAL Checklist when used with older people with dementia. A postal questionnaire sent to activity providers assessed content validity. Validity and reliability were measured in a sample of 60 older people with dementia. The questionnaire response rate was 83% (102/122). Most respondents felt no important items were missing. Seven of the nine activities were ranked as ‘very important’ or ‘essential’ by at least 77% of the sample, indicating very good content validity. Correlation with measures of cognition, severity of dementia and activity performance demonstrated strong concurrent validity. Inter-item correlation indicated strong construct validity. Cronbach’s alpha coefficient measured internal consistency as excellent (0.95). All items achieved acceptable test-retest reliability, and the majority demonstrated acceptable inter-rater reliability. We conclude that the PAL Checklist demonstrates adequate validity and reliability when used with older people with dementia and appears a useful tool for a variety of care settings.

Aging Ment Health. 2008 Mar;12(2):202-11.

Wenborn J, Challis D, Pool J, Burgess J, Elliott N, Orrell M.
Department of Mental Health Sciences, University College London, UK.

Assessing the validity and reliability of the Pool Activity Level (PAL) Checklist for use with older people with dementia.

Activity is key to maintaining physical and mental health and well-being. However, as dementia affects the ability to engage in activity, care-givers can find it difficult to provide appropriate activities. The Pool Activity Level (PAL) Checklist guides the selection of appropriate, personally meaningful activities. The aim of this study was to assess the reliability and validity of the PAL Checklist when used with older people with dementia. A postal questionnaire sent to activity providers assessed content validity. Validity and reliability were measured in a sample of 60 older people with dementia. The questionnaire response rate was 83% (102/122). Most respondents felt no important items were missing. Seven of the nine activities were ranked as ‘very important’ or ‘essential’ by at least 77% of the sample, indicating very good content validity. Correlation with measures of cognition, severity of dementia and activity performance demonstrated strong concurrent validity. Inter-item correlation indicated strong construct validity. Cronbach’s alpha coefficient measured internal consistency as excellent (0.95). All items achieved acceptable test-retest reliability, and the majority demonstrated acceptable inter-rater reliability. We conclude that the PAL Checklist demonstrates adequate validity and reliability when used with older people with dementia and appears a useful tool for a variety of care settings.

Aging Ment Health. 2008 Mar;12(2):202-11.

Wenborn J, Challis D, Pool J, Burgess J, Elliott N, Orrell M.
Department of Mental Health Sciences, University College London, UK.

Altered natural killer cell subset distributions in resolved and persistent hepatitis C virus infection following single source exposure.

BACKGROUND: Natural killer (NK) cells may be impaired in patients with persistent hepatitis C virus (HCV) infection, but studies to date have yielded inconsistent findings due to patient and virus heterogeneity and difficulties obtaining appropriate controls. AIMS: To overcome these variables, we have examined numbers, phenotypes, cytotoxic activities and cytokine profiles of circulating NK cells from Irish females who acquired infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source and matched controls. RESULTS: Comparing 29 women who developed persistent infection with 21 who spontaneously resolved infection and 26 controls, we found that NK cell numbers were consistently lower in the persistently-infected group (p=0.02 and 0.002). This decrease was due to depletions of NK cells expressing low levels of CD56 (CD56dim NK cells; p=0.004 and 0.0001), whilst CD56bright NK cells were expanded (p=0.004 and 0.0001). Compared to HCV resolvers, CD56dim NK cells from persistently-infected patients less frequently expressed CD16 and more frequently expressed NKG2A/C/E. These phenotypic changes did not significantly affect natural or interleukin-2-induced cytotoxicity by peripheral blood mononuclear cells against K562 and Daudi targets. Greater frequencies of CD56bright NK cells from chronic HCV patients produced interferon-gamma compared to HCV responders (p=0.05) and controls (p=0.0001) after phorbol ester stimulation in vitro. CONCLUSIONS: Alterations in NK subset distributions in chronic HCV infection may explain why previous reports of impaired NK cell functions were difficult to confirm. Altered NK cell functions may contribute to impaired cellular immune responses and chronicity of disease following HCV infection.

Golden-Mason L, Madrigal-Estebas L, McGrath E, Conroy MJ, Ryan EJ, Hegarty JE, O\’Farrelly C, Doherty DG.

Republic of Ireland.

Helminths as Governors of Inflammatory Bowel Disease.

The incidence of the inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn\’s disease (CD) markedly increased in industrialised countries during the past decades. In contrast to these countries where helminthosis are rare, IBD is still uncommon in global areas where most people carry worms. Thus lack of exposure to parasites may critically contribute to the risk of IBD. In a recent article in Gut, Summers et al. demonstrated efficacy of treatment with Trichuris suis in active CD (Gut 2005;54:87-90). Trichuris suis was additionally shown to be effective in UC in a randomized trial carried out by the same group. Both studies did not address mechanisms of action. Here we present a real life scenario, which supports the impact of helminths in the prevention of IBD, and provide a rationale for the mechanisms of action.

Buening J, Homann N, von Smolinski D, Borcherding F, Noack F, Stolte M, Kohl M, Lehnert H, Ludwig D.

Department of Internal Medicine I, Germany.

Gastroesophageal reflux and aspiration of gastric contents in adult patients with cystic fibrosis.

GOR is increased in cystic fibrosis (CF), however, its prevalence, characteristics, association with gastric aspiration and respiratory impact are not well characterized. We investigated acid and weakly acidic (WA) reflux, aspiration and respiratory ymptoms/function in adult CF patients. METHODS: Thirty-three CF patients [19men; 29(18-55) years, (10 post LTx)] underwent impedance-pH monitoring for detection of acid (pH<4) and WA GOR (pH4-7). In 16 patients cough was objectively recorded with oesophageal manometry, and the Symptom Association Probability (SAP) was calculated. Saliva and Bronchoalveolar Lavage Fluid (BALF) were tested for bile acids (BA). RESULTS: Twenty-eight patients had increased GOR (21acid, 5WA and 2acid+WA) and 10 had a positive SAP for reflux-cough. GOR parameters were similar in non-LTx and post-LTx CF patients. The sequence reflux-cough was significantly more common than cough-reflux. 16/38 patients had BA in saliva and 6/10 in BALF and this was almost exclusively observed in patients with genotype DF508/DF508. Only 12/28 with increased GOR and 9/22 with BA in saliva/BALF had typical reflux symptoms. There was a positive correlation (r=0.53, p=0.03) between oesophageal acid exposure and cough. SAP-positive patients with for reflux-cough had a lower lung function than SAP-negative patients. CONCLUSION: Increased GOR is prevalent in CF and not secondary to cough. Acid GOR is common, but WA GOR may also occur. CF patients have a high risk for aspiration and reflux seems to be associated with more cough and poorer lung function. Outcome studies with intense anti-reflux therapy are needed to confirm the deleterious role of reflux in CF progression.

Blondeau K, Dupont L, Mertens V, Verleden G, Malfroot A, Vandenplas Y, Hauser B, Sifrim D.

K.U.Leuven,, Belgium.

Correction.

Implementation of electronic patient records in a sexual health clinic.

Brook MG, Davies J, McSorley J, Murphy S.

Patrick Clements GUM Centre, Central Middlesex Hospital, Acton Lane, London, NW10 7 NS, UK. gary.brook@nwlh.nhs.uk