Origins of serum semicarbazide-sensitive amine oxidase

Semicarbazide-sensitive amine oxidases (SSAO) are enzymes that are capable of deaminating primary amines to produce aldehyde, ammonia, and hydrogen peroxide. This activity has been associated with vascular adhesion protein-1 (VAP-1) and is found in the serum, endothelium, adipose, and smooth muscle of mammals. Circulating SSAO activity is increased in congestive heart failure, diabetes, and inflammatory liver diseases. To investigate the origin of circulating SSAO activity, two transgenic mouse models were created with full-length human VAP-1 (hVAP-1) expressed on either endothelial (mTIEhVAP-1) or adipose tissues (aP2hVAP-1), with tie-1 and adipocyte P2 promoters, respectively. Under normal conditions a circulating form of hVAP-1 was found at high levels in the serum of mice with endothelium-specific expression and at low levels in the serum of mice with adipose specific expression. The level of circulating hVAP-1 in the transgenic mice varied with gender, transgene zygosity, diabetes, and fasting. Serum SSAO activity was absent from VAP-1 knockout mice and endothelial cell-specific expression of human VAP-1 restored SSAO activity to the serum of VAP-1 knockout mice. Together, these experiments show that in the mouse VAP-1 is the only source of serum SSAO, that under physiological conditions vascular endothelial cells can be a major source of circulating VAP-1 protein and SSAO, and that serum VAP-1 can originate from both endothelial cells and adipocytes during experimental diabetes. An increased endothelial cell capacity for lymphocyte binding and altered expression of redox-sensitive proteins was also associated with the mTIEhVAP-1 transgene.     

The relative validity of reports of food intake of Dutch and Finnish boys aged 8 and 9 years

Two studies were carried out to assess the relative validity of the techniques used in measuring the food intake during school lunch or home dinner of 30 Finnish and 68 Dutch boys aged 8 and 9 years. For each of the 30 Finnish boys, duplicate portions of three lunches provided to the boys were collected by a non-participating observer. Nutrient intakes were calculated with the use of a food composition table, and the results were compared with those from the records that were kept by the boys' mothers. For each of the 68 Dutch boys, duplicate portions of the hot meal, taken at home, were collected and analyzed chemically. The results were compared with those from the records that were kept by the boys' mothers. The mean values for the absolute intakes of energy and nutrients for the boys from both Finland and The Netherlands as reported by the boys themselves or their mothers were generally higher (15% to 35%) than those measured by chemical analysis of a duplicate portion or calculated from a weighed portion as collected by a non-participating observer. However, the results for the relative proportions of energy generally showed closer agreement (range of difference, +11% to -15%). The authors found in this study that collection of duplicate portions of food resulted in lower (3% to 15%) recorded food intakes in comparison with measurements recorded for meals consumed on other days.     

Gln27Glu variant of Beta2-adrenoceptor gene affects male type fat accumulation in women

Background  

The β₂-adrenergic receptor (BAR2) is the main lipolytic receptor in white human adipose tissue. There is a functional glutamine 27 glutamic acid (Gln27Glu, rs 1042714) polymorphism in its gene, which has been variably associated with body mass index. This gene variant may be associated with male-type adiposity in women and thus increased cardiovascular risk. We investigated whether the BAR2 Gln27Glu polymorphism is associated with visceral fat and coronary intima thickness in women.     

Simultaneous Measurement of Contraction and Calcium Transients in Stem Cell Derived Cardiomyocytes

Induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) provide a powerful platform for disease modeling and drug development in vitro. Traditionally, electrophysiological methods or fluorescent dyes (e.g. calcium) have been used in their functional characterization. Recently, video microscopy has enabled non-invasive analysis of CM contractile motion. Simultaneous assessments of motion and calcium transients have not been generally conducted, as motion detection methods are affected by changing pixel intensities in calcium imaging. Here, we present for the first time a protocol for simultaneous video-based measurement of contraction and calcium with fluorescent dye Fluo-4 videos without corrections, providing data on both ionic and mechanic activity. The method and its accuracy are assessed by measuring the effect of fluorescence and background light on transient widths and contraction velocity amplitudes. We demonstrate the method by showing the contraction-calcium relation and measuring the transient time intervals in catecholaminergic polymorphic ventricular tachycardia patient specific iPSC-CMs and healthy controls. Our validation shows that the simultaneous method provides comparable data to combined individual measurements, providing a new tool for measuring CM biomechanics and calcium simultaneously. Our results with calcium sensitive dyes suggest the method could be expanded to use with other fluorescent reporters as well.     

Increased incidence of Hirschsprung's disease in patients with hypoplastic left heart syndrome—a common neural crest-derived etiology?

Background

The enteric ganglions and the outflow tract of the heart originate from the neural crest. Impaired migration or differentiation of the neural crest cells causes Hirschsprung's disease (HD) and results in the development of cardiac outflow tract malformations. We hypothesize that the incidence of HD and bowel disorders associated with HD are increased in patients with hypoplastic left heart syndrome (HLHS) including left cardiac outflow tract obstruction.

Methods

All consecutive patients treated for HLHS at our institution during 1969 to 2005 were retrospectively reviewed. The number of patients with histologically confirmed HD or clinical findings characteristic of HD such as constipation and delayed meconium were recorded from the patient records.

Results

A total of 113 patients (65 males) were identified. At the time of survey, 57 patients (51%) were alive. Overall, there were 26 (23%) patients with constipation, and 9/23 (39%) had delayed passage of meconium after 48 hours. Despite frequent bowel disorders only 4 (3.5%) patients had undergone histologic examination of the rectum. Hirschsprung's disease was detected in 3 patients (95% confidence interval, 0.62-8.77). The expected number of HD cases in the study population was 0.026 giving 117-fold significant increase in the incidence of HD among patients with HLHS when compared to general Finnish population.

Conclusions

The incidence of HD is increased in patients with HLHS. These results point to a common neural crest-derived embryologic origin of HD and HLHS and warrant further studies.     

Alexithymia and occupational burnout are strongly associated in working population

OBJECTIVE: The relationship between alexithymia and occupational burnout has not previously been studied. We investigated the association between alexithymia and occupational burnout in a representative nationwide population health study. METHODS: This study was a part of the Finnish Health 2000 Study. The nationally representative sample comprised 3322 employees aged 30-64 years. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20) and occupational burnout with the Maslach Burnout Inventory-General Survey. Sociodemographic and health-related variables including depression were treated as confounders in the logistic regression analyses, which were performed alternately with TAS-20 total score and the scores of the three TAS-20 factor scales as alexithymia variables. RESULTS: Alexithymia and its three facets were significantly associated with occupational burnout even when controlled for confounding factors. CONCLUSIONS: Even though both alexithymia and depression are associated with burnout, alexithymia may be an independent risk factor for occupational burnout.