Biomarkers of abdominal aortic aneurysm progression. Part 2: inflammation

Defining progression of abdominal aortic aneurysm (AAA) is complicated by several factors, including measurement error, duration of follow-up, and the imaging modality used to assess AAA expansion. Investigations of biomarkers of AAA progression should be standardized so that valid comparisons can be made. Previous research has shown some promising advances towards identifying a reliable and individual predictor of AAA progression. In this second part of our Review on biomarkers of AAA progression, we examine direct and indirect markers of inflammation including various cytokines, C-reactive protein, activators of tissue plasminogen activator and urokinase plasminogen activator, and osteopontin

Biomarkers of AAA progression. Part 1: extracellular matrix degeneration

Abdominal aortic aneurysm (AAA) is an important health problem. Elective surgical treatment is recommended on the basis of an individual's risk of rupture, which is predicted by AAA diameter. However, the natural history of AAA differs between patients and a reliable and individual predictor of AAA progression (growth and expansion rates) has not been established. Several circulating biomarkers are candidates for an AAA diagnostic tool. However, they have yet to meet the triad of biomarker criteria: biological plausibility, correlation with AAA progression, and prediction of treatment effect on disease outcome. Circulating levels of markers of extracellular matrix degeneration, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase-alpha1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin-antiplasmin complexes and tissue plasminogen activator, have been correlated with AAA progression and have biological plausibility. Although studies of these markers have shown promising results, they have not yet led to a clinically applicable biomarker. In future studies, adjustment for initial AAA size, smoking history and the measurement error for determination of AAA size, among other variables, should be taken into account. A large, prospective, standardized, follow-up study will be needed to investigate multiple circulating biomarkers for their potential role in the prediction of AAA progression, followed by a study to investigate the effect of treatment on the circulating levels of biomarkers

Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients

In vitro and in vivo animal studies have reported strong insulin-like or insulin-potentiating effects after cinnamon administration. Recently, a human intervention study showed that cinnamon supplementation (1 g/d) strongly reduced fasting blood glucose concentration (30%) and improved the blood lipid profile in patients with type 2 diabetes. The objective of this study was to investigate the effects of cinnamon supplementation on insulin sensitivity and/or glucose tolerance and blood lipid profile in patients with type 2 diabetes. Therefore, a total of 25 postmenopausal patients with type 2 diabetes (aged 62.9 +/- 1.5 y, BMI 30.4 +/- 0.9 kg/m(2)) participated in a 6-wk intervention during which they were supplemented with either cinnamon (Cinnamomum cassia, 1.5 g/d) or a placebo. Before and after 2 and 6 wk of supplementation, arterialized blood samples were obtained and oral glucose tolerance tests were performed. Blood lipid profiles and multiple indices of whole-body insulin sensitivity were determined. There were no time x treatment interactions for whole-body insulin sensitivity or oral glucose tolerance. The blood lipid profile of fasting subjects did not change after cinnamon supplementation. We conclude that cinnamon supplementation (1.5 g/d) does not improve whole-body insulin sensitivity or oral glucose tolerance and does not modulate blood lipid profile in postmenopausal patients with type 2 diabetes. More research on the proposed health benefits of cinnamon supplementation is warranted before health claims should be made. AD - Department of Clinical Chemistry, Academic Hospital Maastricht, The Netherlands

SGA and measures for muscle mass and strength in surgical Vietnamese patients

OBJECTIVE: This study compared the outcome of the Subjective Global Assessment (SGA) in preoperative surgical patients with objective measurements of muscle mass and strength and with biochemical data. A secondary aim was to test the influence of inflammatory activity on muscle strength. METHODS: Two hundred seventy-four consecutive patients who were admitted for elective major abdominal surgery were assessed using the SGA, anthropometry, muscle strength, and laboratory measurements (hemoglobin, protein, albumin, C-reactive protein, and lymphocytes). Normal values for midarm muscle circumference (MAMC) and handgrip strength were obtained in a healthy control group. For all other variables, normal values available for the Vietnamese population were used. RESULTS: Of 274 patients (151 men, 123 women) assessed, 61 (22.3%) were classified as SGA class A (well nourished), 97 patients (35.4%) as class B (moderately malnourished), and 116 patients (42.3%) as class C (severely malnourished). There were significant differences in age, body weight, percentage of weight loss, triceps skinfold thickness, MAMC, and serum albumin across the three SGA classes. Almost all patients rated class A had normal MAMC and handgrip strength. However, a large proportion of patients rated as B or C also had normal MAMC and handgrip strength (38% of men, 50% of women). Handgrip strength per square meter correlated with serum albumin (r = 0.278, P < 0.001) and this correlation persisted when handgrip strength was controlled for MAMC (r = 0.296, P < 0.001 in men; r = 0.237, P < 0.01 in women). CONCLUSION: The SGA correctly identifies patients with normal muscle mass and strength but a substantial number of patients rated SGA B or C have normal muscle mass and strength. Muscle strength is not only positively associated with muscle mass but also negatively with inflammatory activity

Characterization of the perfusate proteome of human donor kidneys

BACKGROUND: Preservation of deceased donor kidneys by hypothermic machine perfusion results in superior transplant outcomes as compared with static cold storage and provides the opportunity to measure biomarkers of cellular injury in perfusate samples. Identification of biomarkers predicting early graft dysfunction so far has met with limited success. METHODS: Two-dimensional difference gel electrophoresis and mass spectrometry were used to explore the proteome of perfusate samples from machine-perfused human donor kidneys (N = 18) and to discover novel biomarkers of ischaemic acute kidney injury. RESULTS: Thirty-two protein spots were successfully identified, representing 19 unique proteins that were derived from renal tissue and from residual plasma in the renal microcirculation. Two unidentified protein spots were significantly up-regulated, whereas one protein spot--identified as haptoglobin--was significantly down-regulated in the perfusate of ischaemically injured kidneys from donors after cardiac death as compared with kidneys from brain-dead donors who had not suffered warm ischaemic injury. Furthermore, two protein spots were up-regulated in kidneys that never functioned after transplantation, whereas one spot was up-regulated--identified as alpha1-antitrypsin--in kidneys with delayed graft function. CONCLUSIONS: We provide the first description of the renal perfusate proteome and present preliminary evidence of differentially expressed biomarkers in human donor kidneys with different levels of acute ischaemic injury. Their diagnostic value for the selection of marginal kidneys in clinical transplantation should be determined in future studies

The muscle protein synthetic response to carbohydrate and protein ingestion is not impaired in men with longstanding type 2 diabetes.

Protein ingestion stimulates muscle protein synthesis and improves net muscle protein balance. Insulin resistance has been suggested to result in a reduced muscle protein synthetic response to food intake. As such, we hypothesized that type 2 diabetes patients have a impaired muscle protein synthetic response to food ingestion. To test this hypothesis, 10 male type 2 diabetes patients using their normal oral glucose-lowering medication (68 +/- 2 y) and 10 matched, normoglycemic men (65 +/- 2 y) were randomly assigned to 2 crossover treatments in which whole body and muscle protein synthesis were measured following the consumption of either carbohydrate (CHO) or carbohydrate with a protein hydrolysate (CHO+PRO). Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied and blood and muscle samples were collected to assess whole-body protein balance and mixed muscle protein fractional synthetic rate over a 6-h period. Whole-body phenylalanine and tyrosine flux were higher after the CHO+PRO treatment compared with the CHO treatment in the diabetes and control group (P <0.01). Protein balance was negative following CHO but positive following CHO+PRO treatment in both groups. Muscle protein synthesis rates were higher in both groups following the CHO+PRO (0.086 +/- 0.014%/h) treatment than in the CHO treatment (0.040 +/- 0.003%/h; P <0.01) with no difference between the diabetes patients and normoglycemic controls. We conclude that the muscle protein synthetic response to CHO or CHO+PRO ingestion is not substantially impaired in longstanding, type 2 diabetes patients treated with oral blood glucose-lowering medication

FSH isoform pattern in classic galactosemia

Female classic galactosemia patients suffer from primary ovarian insufficiency (POI). The cause for this long-term complication is not fully understood. One of the proposed mechanisms is that hypoglycosylation of complex molecules, a known secondary phenomenon of galactosemia, leads to FSH dysfunction. An earlier study showed less acidic isoforms of FSH in serum samples of two classic galactosemia patients compared to controls, indicating hypoglycosylation. In this study, FSH isoform patterns of five classic galactosemia patients with POI were compared to the pattern obtained in two patients with a primary glycosylation disorder (phosphomannomutase-2-deficient congenital disorders of glycosylation, PMM2-CDG) and POI, and in five postmenopausal women as controls. We used FPLC chromatofocussing with measurement of FSH concentration per fraction, and discovered that there were no significant differences between galactosemia patients, PMM2-CDG patients and postmenopausal controls. Our results do not support that FSH dysfunction due to a less acidic isoform pattern because of hypoglycosylation is a key mechanism of POI in this disease