Biokinetics and radiation dosimetry for patients undergoing a glycerol tri[1-14C]oleate fat malabsorption breath test.

The glycerol tri[1-14C]olein test for fat malabsorption was carried out in two male volunteers and measurements of the loss of 14C in expired air, urine and faeces and the retention of 14C in biopsy samples of abdominal fat were made using accelerator mass spectrometry. Exhalation accounted for 73% and 55% of the administered activity and could be described by three-component exponential functions with halftimes of about 1h, 2 days and 150 days, respectively. Urinary excretion accounted for 24% of the administered activity, almost all during the first 24h after administration; about 2% was excreted in the faeces in 48h. The halftime of retention of 14C in fat ranged from 137 to 620 days. Absorbed dose calculations indicate that for a normal adult the largest dose, 1.5-7.0mGy/MBq is received by the adipose tissue, and that the effective dose is 0.3-0.5mSv/MBq. It is concluded that no restrictions need to be placed on radiation safety grounds on the administration of 0.05-0.1MBq 14C-triolein for the triolein breath test.     

Progressive delayed-onset dystonia after cerebral anoxic insult in adults.

The basal ganglia, especially the globi pallidi (GP), are highly vulnerable to generalized cerebral anoxia/hypoxia. We report on 2 new cases with delayed-onset generalized dystonia due to cerebral anoxia. The onset of dystonia in both of our patients was delayed by about 2 months. In both cases, the unusual feature was the progressive worsening and the spread of dystonia over many years after delayed onset. Dystonia progressed for 16 years in Case 1 and for 4 years in Case 2. Furthermore, initial magnetic resonance imaging (MRI) scan of Case 1 showed mild changes of the internal capsule sparing the basal ganglia. Years later, in line with clinical progression, the follow-up MRI scan showed isolated bilateral lesions involving the entire GP. MRI scans in Case 2 showed bilateral lesions of caudate and lentiform nuclei. There may be several mechanisms underlying delayed and progressive symptoms after time-limited brain anoxia. We hypothesize that anoxia-induced excitotoxicity resulting in mitochondrial dysfunction and subsequent apoptosis may explain, at least partly, the delayed-onset and progressive extrapyramidal syndromes seen in these patients.     

Tissue Oxygen Demand in Regulation of the Behavior of the Cells in the Vasculature

The control of arteriolar diameters in microvasculature has been in the focus of studies on mechanisms matching oxygen demand and supply at the tissue level. Functionally, important vascular elements include EC, VSMC, and RBC. Integration of these different cell types into functional units aimed at matching tissue oxygen supply with tissue oxygen demand is only achieved when all these cells can respond to the signals of tissue oxygen demand. Many vasoactive agents that serve as signals of tissue oxygen demand have their receptors on all these types of cells (VSMC, EC, and RBC) implying that there can be a coordinated regulation of their behavior by the tissue oxygen demand. Such functions of RBC as oxygen carrying by Hb, rheology, and release of vasoactive agents are considered. Several common extra‐ and intracellular signaling pathways that link tissue oxygen demand with control of VSMC contractility, EC permeability, and RBC functioning are discussed.     

Artefactual effects of lipid-based cell transfection reagents on AβPP processing and Aβ production

The study of amyloidogenic β-amyloid precursor protein (AβPP) metabolism and amyloid β protein (Aβ) production has been a major focus of Alzheimer's disease (AD) neuropathogenesis research. Cell transfection is a commonly employed method for assessing the effects of various genes on AβPP processing and Aβ production. Certain cell transfection reagents utilize lipid-based formulations that could potentially affect AβPP processing and Aβ production. Thus, we set out to assess the effects of cell transfection reagents with lipid formulations (TKO, FuGene6, RNAifect) on AβPP processing and Aβ level in H4 human neuroglioma cells overexpressing human AβPP. We found both TKO and RNAifect increase the protein levels of AβPP-C-terminal fragments (CTFs) and Aβ levels, while FuGene6 increases the protein levels of AβPP-CTFs without altering Aβ level. In contrast, electroporation-based cell transfection does not affect AβPP processing and Aβ production in our studies. These results suggest for the first time that lipid-based cell transfection reagents may artefactually affect AβPP processing and Aβ production, thereby confounding studies aimed at assessing the effects of transfected genes on AβPP metabolism.     

Mannose-binding lectin as a risk factor for acute coronary syndromes

Background. Mannose-binding lectin (MBL) is a multifunctional protein involved in innate immunity. We tested whether MBL and elevated viral and bacterial antibodies were risk factors for acute coronary events.

Design. Controlled cohort study.

Methods. A total of 354 patients with unstable angina pectoris (UA) or acute myocardial infarction (AMI) were compared with 334 paired controls.

Results. Enterovirus titres were associated with increased risk of UA (odds ratio 10.04, P<0.001) and AMI (odds ratio 3.18, P=0.003), but titres did not correlate with either MBL concentration or genotype. Chlamydiapneumoniae heat shock protein 60 IgG concentrations were also associated with increased risk of UA (odds ratio 1.63, P=0.049). Compared to asymptomatic controls, patients had lower complement C3 serum concentrations (P<0.001), higher MBL serum concentration, and more frequently had MBL genotypes that determined high MBL levels (P<0.001). High MBL genotypes had odds ratios of 1.16 (P=0.010) for UA and 1.12 (P=0.007) for AMI. The elevation of MBL concentrations in the acute phase correlated with MBL concentrations after recovery (r=0.85, P<0.001).

Conclusions. Elevated microbial titres, indicating an on-going inflammation, were associated with cardiovascular events. MBL might have a dual role both decreasing susceptibility to infections and increasing the risk of acute coronary syndromes.     

FIGO 1988 versus 2009 staging for endometrial carcinoma: a comparative study on prediction of survival and stage distribution according to histologic subtype

Objective

The surgical staging system for endometrial carcinoma developed by International Federation of Gynecology and Obstetrics (FIGO) in 1988 was revised in 2009. Given the importance of continuous validation of the prognostic performance of staging systems, we analyzed the disease specific survival for patients with endometrial carcinoma using FIGO 1988 and 2009 systems. Further, the stage distribution of endometrioid and nonendometrioid carcinomas was studied.

Methods

Eight hundred twenty-one women with endometrial carcinoma were retrospectively staged using FIGO 1988 and 2009 systems.

Results

FIGO 1988 IC was associated with an inferior survival compared with IA-IB. Survival overlapped for 1988 IA and IB, for 1988 IC and IIA, and for 2009 IB and II. FIGO 2009 IA-II patients with negative peritoneal cytology had a superior survival compared with 1988 IIIA patients with positive cytology only. The survival was similar for 1988 IIIA with positive cytology only and for 2009 IIIA. Cox proportional hazards model recognized grade 3 endometrioid and nonendometrioid histology, tumor spread beyond the uterine corpus and cervix, and positive peritoneal cytology as significant predictors of death. Among 2009 IIIC substages, the proportion of IIIC2 tumors was higher for nonendometrioid than for endometrioid carcinomas (p=0.003).

Conclusion

Stage I with deep myometrial invasion and stage II endometrial carcinoma seem to have similar survival outcomes. Although positive peritoneal cytology does not alter the stage according to the FIGO 2009 system, it should be considered a poor prognostic sign. The high proportion of nonendometrioid carcinomas in the stage IIIC2 category may reflect different patterns of retroperitoneal spread among tumors with different histologic subtypes.     

Individual and combined toxicity of T‐2 toxin and deoxynivalenol on human C‐28/I2 and rat primary chondrocytes

Deoxynivalenol (DON) and T‐2 toxin are prevalent mycotoxin contaminants in the food and feed stuffs worldwide, with non‐negligible co‐contamination and co‐exposure conditions. Meanwhile, they are considerable risk factors for Kashin‐Beck disease, a chronic endemic osteochondropathy. The aim of this study was to investigate the individual and combined cytotoxicity of DON and T‐2 toxin on proliferating human C‐28/I2 and newborn rat primary costal chondrocytes by MTT assay. Four molar concentration combination ratios of DON and T‐2 toxin were used, 1:1 for R1 mixture, 10:1 for R10, 100:1 for R100 and 1000:1 for R1000. The toxicological interactions were quantified by the MixLow method. DON, T‐2 toxin, and their mixtures all showed a clear dose‐dependent toxicity for chondrocytes. The cytotoxicity of T‐2 toxin was 285‐fold higher than DON was in human chondrocytes, and 22‐fold higher in the rat chondrocytes. The combination of DON and T‐2 toxin was significantly synergistic at middle and high level concentrations of R10 mixtures in rat chondrocytes, but significantly antagonistic at the low concentrations of R100 mixtures in both cells and at the middle concentrations of R1000 mixtures in rat chondrocytes. These results indicated that the combined toxicity was influenced by the cell sensitivity for toxins, the difference between the combination ratio and equitoxic ratio, the concentrations and other factors.