11C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia

PURPOSE: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [11C]palmitate injection during fasting and insulin stimulation. METHODS: Plasma [11C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. RESULTS: At 10 min, plasma levels of unchanged [11C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P< or=.03), suggesting faster clearance. Levels of unmetabolized [11C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [11C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92+/-1% and 82+/-6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. CONCLUSION: The study indicates that the redistribution of [11C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG constitute an additional [11C]palmitate source in the modeling of PET data.     

Switching from levodopa to the long-acting dopamine D2/D3 agonist piribedil reduces the expression of dyskinesia while maintaining effective motor activity in MPTP-treated primates

BACKGROUND: The control of motor complications following dopaminergic medication in late-stage Parkinson disease remains problematic. OBJECTIVE: We now investigate the potential of oral administration of the long-acting dopamine D2/D3 agonist piribedil to decrease the expression of dyskinesia induced by prior exposure to levodopa in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated primates. METHODS: MPTP-treated common marmosets were treated with equieffective doses of levodopa (10.0-12.5 mg/kg PO, twice daily) or piribedil (3.0-4.0 mg/kg PO, once daily) for 30 days and then switched to the alternative treatment for a further 35 days. RESULTS: Levodopa administration markedly improved motor function, but dyskinesia rapidly appeared and intensified as treatment progressed. Administration of piribedil produced a similar reversal of MPTP-induced motor deficits but with comparatively mild dyskinesia. On switching from levodopa to piribedil, the intensity of dyskinesia decreased without altering the improvement in motor deficits. However, on switching from piribedil to levodopa, the rapid increase in dyskinesia despite the improvement in motor function being maintained suggests that piribedil also primes for but does not markedly express dyskinesia. CONCLUSION: The study confirms the low dyskinesia expression resulting from piribedil treatment compared with an equieffective dose of levodopa. Importantly, the results show that switching from levodopa to piribedil rapidly results in a sustained decrease in dyskinesia intensity.     

Toxicological effects of emission particles from fossil- and biodiesel-fueled diesel engine with and without DOC/POC catalytic converter

There is increasing demand for renewable energy and the use of biodiesel in traffic is a major option when implying this increment. We investigated the toxicological activities of particulate emissions from a nonroad diesel engine, operated with conventional diesel fuel (EN590), and two biodiesels: rapeseed methyl ester (RME) and hydrotreated fresh vegetable oil (HVO). The engine was operated with all fuels either with or without catalyst (DOC/POC). The particulate matter (PM(1)) samples were collected from the dilution tunnel with a high-volume cascade impactor (HVCI). These samples were characterized for ions, elements, and polycyclic aromatic hydrocarbon (PAH) compounds. Mouse RAW264.7 macrophages were exposed to the PM samples for 24 h. Inflammatory mediators, (TNF-α and MIP-2), cytotoxicity, genotoxicity, and oxidative stress (reactive oxygen species [ROS]) were measured. All the samples displayed mostly dose-dependent toxicological activity. EN590 and HVO emission particles had larger inflammatory responses than RME-derived particles. The catalyst somewhat increased the responses per the same mass unit. There were no substantial differences in the cytotoxic responses between the fuels or catalyst use. Genotoxic responses by all the particulate samples were at same level, except weaker for the RME sample with catalyst. Unlike other samples, EN590-derived particles did not significantly increase ROS production. Catalyst increased the oxidative potential of the EN590 and HVO-derived particles, but decreased that with RME. Overall, the use of biodiesel fuels and catalyst decreased the particulate mass emissions compared with the EN590 fuel. Similar studies with different types of diesel engines are needed to assess the potential benefits from biofuel use in engines with modern technologies.     

Downregulation of tyrosine hydroxylase phenotype after AAV injection above substantia nigra: Caution in experimental models of Parkinson’s disease

Adeno-associated virus (AAV) vector-mediated delivery of human α-synuclein (α-syn) gene in rat substantia nigra (SN) results in increased expression of α-syn protein in the SN and striatum which can progressively degenerate dopaminergic neurons. Therefore, this model is thought to recapitulate the neurodegeneration in Parkinson's disease. Here, using AAV to deliver α-syn above the SN in male and female rats resulted in clear expression of human α-syn in the SN and striatum. The protein was associated with moderate behavioral deficits and some loss of tyrosine hydroxylase (TH) in the nigrostriatal areas. However, the immunohistochemistry results were highly variable and showed little to no correlation with behavior and the amount of α-syn present. Expression of green fluorescent protein (GFP) was used as a control to monitor gene delivery and expression efficacy. AAV-GFP resulted in a similar or greater TH loss compared to AAV-α-syn and therefore an additional vector that does not express a protein was tested. Vectors with double-floxed inverse open reading frame (DIO ORF) encoding fluorescent proteins that generate RNA that is not translated also resulted in TH downregulation in the SN but showed no significant behavioral deficits. These results demonstrate that although expression of wild-type human α-syn can cause neurodegeneration, the variability and lack of correlation with outcome measures are drawbacks with the model. Furthermore, design and control selection should be considered carefully because of conflicting conclusions due to AAV downregulation of TH, and we recommend caution with having highly regulated TH as the only marker for the dopamine system.     

Congenital diaphragmatic hernia: a scientometric analysis of the global research activity and collaborative networks

Despite a growing interest to clinicians and scientists, there is no comprehensive study that examines the global research activity on congenital diaphragmatic hernia (CDH). A search strategy for the Web of Science? database was designed to identify scientific CDH publications. Research output of countries, institutions, individual authors, and collaborative networks was analyzed. Semi-qualitative research measures including citation rate and h-index were assessed. Choropleth mapping and network diagrams were employed to visualize results. A total of 3669 publications were found, originating from 76 countries. The largest number was published by the USA (n?=?1250), the UK (n?=?279), and Canada (n?=?215). The USA combined the highest number of cooperation articles (n?=?152), followed by Belgium (n?=?115) and the Netherlands (n?=?93). The most productive collaborative networks were established between UK/Belgium (n?=?53), Belgium/Spain (n?=?47), and UK/Spain (n?=?34). Canadian publications received the highest average citation rate (22.8), whereas the USA had the highest country-specific h-index (72). Eighty-five (2.3%) articles were published by international multicenter consortiums and national research networks. The most productive institutions and authors were based in North America and Europe. Over the past decades, CDH research has increasingly become multidisciplinary and numerous innovative therapeutic strategies were introduced. CDH-related research has constantly been progressing, involving today many disciplines with main research endeavors concentrating in a few high-income countries. Recent advances in prenatal interventions and regenerative medicine therapy hold the promise of improving CDH outcome in the 21st century. International collaborations and translational research should be strengthened to allow further evolution in this field.     

Estimation of maximal heart rate using the relationship between heart rate variability and exercise intensity in 40–67 years old men

Large interindividual variation in maximal heart rate (HR_max) may not be accounted for by age alone. In order to evaluate a novel method in the prediction of HR_max, this study examined the profile of HR variability (HRV) during exercise in 40–67 years old men (n = 74). R–R intervals were recorded during supine rest and during a graded exercise test by cycle ergometry until exhaustion. A third-degree polynomial function was fitted to the HRV data recorded during exercise to represent the HRV profile of each subject. The instantaneous beat-to-beat R–R interval variability (SD1), high (HF) and low frequency power decreased between all consecutive exercise intensities (P < 0.033). The relationship between HR_max and a variable illustrating the declining rate of HF (HR_HF50%) was stronger (r = 0.50, P < 0.001) than between HR_max and age (r = −0.36, P < 0.01). The regression analysis showed that a more accurate estimation of HR_max was attained when HRV was used in the equation in addition to age: HR_max = 160.633–0.603(age) + 0.441(HR_HF50%) (SEE = 9.8 bpm vs. 11.6 bpm in the equation based on age alone). The decline of HRV during incremental exercise seems to be useful for accurate estimation of maximal heart rate.     

Trends in self-reported sleep duration and insomnia-related symptoms in Finland from 1972 to 2005: a comparative review and re-analysis of Finnish population samples

A hypothesis concerning habitual sleep reduction and its adverse consequences among general population in modern societies has received wide publicity in the mass media, although scientific evidence supporting the hypothesis is scarce. Similarly, there is an extensively distributed belief, at least in Finland, that the prevalence of insomnia-related symptoms is increasing, but evidence for this is even sparser. These issues are important because of the known increased risk of mortality and health risks associated with sleep duration deviating from 7 to 8 h. To reveal possible trends in self-reported sleep duration and insomnia-related symptoms, we reanalyzed all available data from surveys carried out in Finland from 1972 to 2005. The main results were that a minor decrease of self-reported sleep duration has taken place in Finland, especially among working aged men. However, the size of the reduction (about 4%) was relatively small, approximately 5.5 min per each 10 years during the 33 years' time interval under study. The proportion of 7 h sleepers has increased and, correspondingly, the proportion of 8 h sleepers has decreased, but the extreme ends of the sleep duration distribution remained unchanged. Tentative evidence suggesting an increase in insomnia-related symptoms among working aged population during the last 10 years was found. In conclusion, the Finnish data during the past 33 years indicate a general decrease in self-reported sleep duration of about 18 min and an increase of sleep complaints, especially among the employed middle-aged population.