Plasma glutamine levels before cardiac surgery are related to post-surgery infections; an observational study.

BACKGROUND: A low plasma glutamine level was found in 34% of patients after elective cardiothoracic surgery. This could be a result of the inflammation caused by surgical stress or the use of extracorporeal circulation (ECC). But it is also possible that plasma glutamine levels were already lowered before surgery and reflect an impaired metabolic state and a higher likelihood to develop complications. In the present study plasma glutamine levels were measured before and after cardiac surgery and we questioned whether there is a relation between plasma glutamine levels and duration of ECC and the occurrence of postoperative infections. METHODS: We performed a single-centre prospective, observational study in a closed-format, 20-bed, mixed ICU in a tertiary teaching hospital. We included consecutive patients after elective cardiac surgery with use of extracorporeal circulation. Blood samples were collected on the day prior to surgery and at admission on the ICU. The study was approved by the local Medical Ethics Committee (Regional Review Committee Patient-related Research, Medical Centre Leeuwarden, nWMO 115, April 28th 2015). RESULTS: Ninety patients were included. Pre-operative plasma glutamine level was 0.42 ± 0.10 mmol/l and post-operative 0.38 ± 0.09 mmol/l (p < 0.001). There was no relation between duration of extracorporeal circulation or aortic occlusion time and changes in plasma glutamine levels. A logistic regression analysis showed a significant correlation between the presence of a positive culture during the post-operative course and pre-operative plasma glutamine levels (p = 0.04). CONCLUSION: Plasma glutamine levels are significantly lower just after cardiac surgery compared to pre-operative levels. We did not find a relation between the decrease in plasma glutamine levels and the duration of extracorporeal circulation or aortic clamp time. There was a correlation between pre-operative plasma glutamine levels and the presence of a positive culture after cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02444780 .

Children with asthma have significantly lower long-term cortisol levels in their scalp hair than healthy children.

AIM: Noninvasive measurement of long-term cortisol levels is a useful way of evaluating the effect of chronic disease on the hypothalamic-pituitary-adrenal axis in children. The aim of this pilot study was to compare hair cortisol levels in children using inhaled corticosteroids for asthma and healthy children and to determine the association with short-term salivary cortisol levels. METHODS: Cortisol levels were measured in the scalp hair and saliva of prepubertal children with asthma (n = 10) and without asthma (n = 10). Asthma control was assessed using an asthma questionnaire and pulmonary function tests. RESULTS: The median (95% CI) cortisol level in the scalp hair of the children with asthma (2.0 pg/mg; 1.4-4.1) was significantly lower than the healthy children (4.3 pg/mg; 1.8-5.9). Morning salivary cortisol levels were significantly lower for the children with asthma (5.9 nmol/L; 3.2-11.1) than the healthy children (9.0 nmol/L; 4.4-31.6). There was no significant association between cortisol levels in hair and saliva. CONCLUSION: Long-term cortisol levels were significantly lower in children with asthma than healthy children. Measuring long-term cortisol levels in scalp hair is an attractive, noninvasive tool that can evaluate the effect of asthma and its treatment on the hypothalamic-pituitary-adrenal axis.

Haemostatic variables during normal menstrual cycle. A systematic review.

For a number of haemostatic factors menstrual cycle variation has been studied. Such variation could have clinical implications for the timing of haemostatic testing in women. It was our objective to systematically review the literature about evidence for timing of haemostatic testing during menstrual cycle.We searched MEDLINE, EMBASE and the Cochrane library to identify studies that measured haemostatic variables [platelet function, von Willebrand factor (VWF), factor VIII (FVIII), factor IX (FIX), factor XI (FXI), factor XIII (FXIII), D-dimer, plasminogen activator inhibitor-I (PAI-I), tissue plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), α2-antiplasmin and fibrinogen] during normal menstrual cycle without hormonal contraceptives. Two investigators independently selected studies, and abstracted data in duplicate. We identified 1,046 studies of which we included 30 studies (25 longitudinal and 5 cross-sectional studies). All studies reported on haemostatic variables during menstrual cycle. Overall, most of the studies found no cyclic variation in VWF, FVIII, FXI, FXIII, fibrinolytic factors (PAI, t-PA, uPA, D-dimer and α2-antiplasmin) and fibrinogen. However, in studies where these variables showed any variation, they reached the lowest levels during menstrual and early follicular phase, especially for VWF, FVIII and platelet function tests. In conclusion, the optimal timing for haemostatic testing during menstrual cycle seems to be menstrual and early follicular phase.

Urinary excretion of 5-hydroxyindoleacetic acid, serotonin and 6-sulphatoxymelatonin in normoserotonemic and hyperserotonemic autistic individuals.

OBJECTIVE: A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production. METHODS: Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals. The relationship of urinary 6-sulfatoxymelatonin (6-SM) excretion to platelet 5-HT, and to urinary 5-HT and 5-HIAA excretion, was also examined. RESULTS: In the hyperserotonemic group, significant increases at trend level in urinary excretion of 5-HIAA (p = 0.061) and 5-HT (p = 0.071) and a significant decrease for 6-SM were found (p = 0.027). The urinary 5-HIAA:5-HT ratio was similar in the normo- versus the hyperserotonemic groups. CONCLUSIONS: The catabolism of 5-HT does not differ in the groups, but greater exposure of the platelet to 5-HT cannot be ruled out as a cause of the platelet hyperserotonemia of autism. Although only trend level significant, the data point to a need for larger studies to examine more thoroughly the relationships between platelet hyperserotonemia, gut 5-HT synthesis and melatonin production.

Brief report: normal intestinal permeability at elevated platelet serotonin levels in a subgroup of children with pervasive developmental disorders in Curaçao (The Netherlands antilles).

This study investigated the relationship between platelet (PLT) serotonin (5-HT) and intestinal permeability in children with pervasive developmental disorders (PDD). Differential sugar absorption and PLT 5-HT were determined in 23 children with PDD. PLT 5-HT (2.0-7.1 nmol/10(9) PLT) was elevated in 4/23 patients. None exhibited elevated intestinal permeability (lactulose/mannitol ratio: 0.008-0.035 mol/mol). PLT 5-HT did not correlate with intestinal permeability or GI tract complaints. PLT 5-HT correlated with 24 h urinary 5-hydroxyindoleacetic acid (5-HIAA; p = .034). Also urinary 5-HIAA and urinary 5-HT were interrelated (p = .005). A link between hyperserotonemia and increased intestinal permeability remained unsupported. Increased PLT 5-HT in PDD is likely to derive from increased PLT exposure to 5-HT. Longitudinal studies, showing the (in)consistency of abnormal intestinal permeability and PLT 5-HT, may resolve present discrepancies in the literature.

Comparative urine analysis by liquid chromatography-mass spectrometry and multivariate statistics: method development, evaluation, and application to proteinuria.

We describe a platform for the comparative profiling of urine using reversed-phase liquid chromatography-mass spectrometry (LC-MS) and multivariate statistical data analysis. Urinary compounds were separated by gradient elution and subsequently detected by electrospray Ion-Trap MS. The lower limit of detection (5.7-21 nmol/L), within-day (2.9-19%) and between-day (4.8-19%) analytical variation of peak areas, linearity (R2: 0.918-0.999), and standard deviation for retention time (<0.52 min) of the method were assessed by means of addition of seven 3-8 amino acid peptides (0-500 nmol/L). Relating the amount of injected urine to the area under the curve (AUC) of the chromatographic trace at 214 nm better reduced the coefficient of variation (CV) of the AUC of the total ion chromatogram (CV = 10.1%) than relating it to creatinine (CV = 38.4%). LC-MS data were processed, and the common peak matrix was analyzed by principal component analysis (PCA) after supervised classification by the nearest shrunken centroid algorithm. The feasibility of the method to discriminate urine samples of differing compositions was evaluated by (i) addition of seven peptides at nanomolar concentrations to blank urine samples of different origin and (ii) a study of urine from kidney patients with and without proteinuria. (i) The added peptides were ranked as highly discriminatory peaks despite significant biological variation. (ii) Ninety-two peaks were selected best discriminating proteinuric from nonproteinuric samples, of which 6 were more intense in the majority of the proteinuric samples. Two of these 6 peaks were identified as albumin-derived peptides, which is in accordance with the early rise of albumin during glomerular proteinuria. Interestingly, other albumin-derived peptides were nondiscriminatory indicating preferential proteolysis at some cleavage sites.

Folate and long-chain polyunsaturated fatty acids in psychiatric disease.

Schizophrenia, autism and depression do not inherit by Mendel's law, and the search for a genetic basis seems unsuccessful. Schizophrenia and autism relate to low birth weight and pregnancy complications, which are associated with developmental adaptations by "programming". Epigenetics might constitute the basis of programming and depend on folate status and one-carbon metabolism in general. Early folate status of patients with schizophrenia might be compromised as suggested by (i) coinciding incidences of schizophrenia and neural tube defects (NTDs) in the Dutch hunger winter, (ii) coinciding seasonal fluctuations in birth of patients with schizophrenia and NTDs, (iii) higher schizophrenia incidence in immigrants and (iv) higher incidence in methylene tetrahydrofolate reductase 677C-->T homozygotes. Recent studies in schizophrenia and autism point at epigenetic silencing of critical genes or chromosomal loci. The long-chain polyunsaturated fatty acids (LCPUFA), arachidonic acid (AA, from meat) and docosahexaenoic acid (fish) are components of brain phospholipids and modulators of signal transduction and gene expression. Patients with schizophrenia and, possibly, autism exhibit abnormal phospholipid metabolism that might cause local AA depletion and impaired eicosanoid-mediated signal transduction. National fish intakes relate inversely with major and postpartum depressions. Five out of six randomized controlled trials with eicosapentaenoic acid (fish) have shown positive effects in schizophrenia, and 4 of 6 were favorable in depression and bipolar disorders. We conclude that folate and LCPUFA might be important in both the etiology and severity of at least some psychiatric diseases.