Subcellular localization of monoglyceride acyltransferase, xanthine oxidation, NADP: isocitrate dehydrogenase and alkaline phosphatase in the mucosa of the guinea-pig small intestine.

1. Rate dependent and isopycnic banding in a zonal rotor were used to analyse the subcellular sites of enzymes in homogenates of guinea-pig small intestinal mucosa. 2, The results demonstrate the following localizations: monoglyceride acyltransferase-microsomal; xanthine oxidase and dehydrogenase-soluble phase, and NADP: isocitrate dehydrogenase-soluble phase and mitochondrial. 3, Alkaline phosphatase is confined to brush borders and is absent from the basolateral plasma membrane. A variable proportion of the activity, up to 40%, is on brush borders which during homogenization break up into particles of reduced density and slow sedimentation rate

Zonal rotor study of the subcellular distribution of acyl-CoA synthetases, carnitine acyl transferases and phosphatidate phosphatase in the guinea-pig small intestine.

Homogenates made from the mucosa of the guinea pig small intestine were fractionated in a zonal rotor by rate and isopycnic centrifugation in sucrose gradients. Density perturbation of endoplasmic reticulum vesicles was done by treating homogenate with pyrophosphate and was analysed by isopyenic centrifugation. Subcellular fractions were analysed for the distribution of markers for brush borders. basolateral plasma membrane. Iysosomes. peroxi. somes. mitochondria. nuclei and endoplasmic reliculum. Fractions werc also analysed for the distribution ofpropionyl-. butyryl-. and palmityl. CoA synthetases. for carnitine acetyl and palmityltransferases. and for phosphatidate phosphatase. Comparison of marker and unknown distributions shows that palmityl- CoA synthetase is located on the endoplasmic reticulum. while propionyl- and butyryl-CoA synthetases and carnitine acetyl and pal. mit)'l transferases are exclusively mitochondrial. I'hosphatidate phosphatase has complex subcellular localisation with activity in brush borders. microsomes (possibly not the endoplasmic reticulum component) and possibly Iysosomes

Intestinal peroxisomes of goldfish (Carrassius auratus) - examination for hydrolase, dehydrogenase and carnitine acetyltransferase activities.

1. Rate sedimentation and isopycnic centrifugation were used to analyse the subcellular sites of enzymes in homogenates of goldfish intestinal mucosa. 2. The results allowed the following allocations to be made: carnitine acetyl transferase-mitochondrial and peroxisomal, xanthine dehydrogenase and NAD: :x-glycerophosphate dehydrogenase soluble phase; NADP: isocitrate dehydrogenase soluble phase and mitochondrial, and 2-naphthyl laurate hydrolase microsomal and/or brush border. 3. Histochemistry confirmed the use of alkaline phosphatase and I-naphthyl acetate esterase as brush border and microsome markers respectively. 4. Urate oxidase, allantoinase, allantoicase, xanthine oxidase and glycollatejlactate oxidase, activities were undetectable, and I-naphthyl palmilale hydrolase was present only as a contaminant from pancreas

Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation

Background: Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH) and insulin-like growth factor I (IGF-1). It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG) is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels. Methods: Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG. Results: One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was pound81,000/QALY and pound212,000/LYG. To reduce this to pound30K/QALY would require a reduction in drug cost by about one third. Conclusion: PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK) for determining cost-effectiveness of therapies were to be applied to PEG it would be considered not to represent good value for money

Five-factor model personality traits in opioid dependence

<p>Abstract</p> <p>Background</p> <p>Personality traits may form a part of the aetiology of opioid dependence. For instance, opioid dependence may result from self-medication in emotionally unstable individuals, or from experimenting with drugs in sensation seekers. The five factor model (FFM) has obtained a central position in contemporary personality trait theory. The five factors are: Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness. Few studies have examined whether there is a distinct personality pattern associated with opioid dependence.</p> <p>Methods</p> <p>We compared FFM personality traits in 65 opioid dependent persons (mean age 27 years, 34% females) in outpatient counselling after a minimum of 5 weeks in buprenorphine replacement therapy, with those in a non-clinical, age- and sex-matched sample selected from a national database. Personality traits were assessed by a Norwegian version of the Revised NEO Personality Inventory (NEO PI-R), a 240-item self-report questionnaire. Cohen's d effect sizes were calculated for the differences in personality trait scores.</p> <p>Results</p> <p>The opioid-dependent sample scored higher on Neuroticism, lower on Extraversion and lower on Conscientiousness (d = -1.7, 1.2 and 1.7, respectively) than the controls. Effects sizes were small for the difference between the groups in Openness to experience scores and Agreeableness scores.</p> <p>Conclusion</p> <p>We found differences of medium and large effect sizes between the opioid dependent group and the matched comparison group, suggesting that the personality traits of people with opioid dependence are in fact different from those of non-clinical peers.</p

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Zonal rotor analysis of the subcellular localization of B-glycero-phosphate dehydrogenase, 1-naphthyl palmitate and 2-napthyl laurate hydrolases in the mucosa of the guinea-pig small intestine.

Whole homogenate of guinea-pig small intestine mucosa was analysed by centrifugation in a zonal rotor. The results indicate that FAD-linked a-glycerophosphate dehydrogenase is localized in the mitochondria and that NAD-linked a-glycerophosphate dehydrogenase is a soluble phase enzyme. An enzyme hydrolysing a.-naphthyl palmitate at an acid pH was localized in the Iysosomes and was activated by 0.1% Triton X-IOO and by freezing and thawing. An alkaline hydrolase acting on .B-naphthyl laurate was localized in the 'microsomes'. The possibility of this enzyme being different from a-naphthyl acetate hydrolase is discussed