Circulating free fatty acids, insulin, and glucose during chemical stimulation of hypothalamus in rats

The aim of this study was to investigate plasma free fatty acids (FFA), insulin, and blood glucose during chemical stimulation of the lateral and ventromedial hypothalamic areas (LHA and VMH) in rats. Therefore male Wistar rats were implanted with bilateral cannulas in the LHA or the VMH and into the left and right jugular veins. Freely moving rats were then infused into the LHA and VMH with norepinephrine (NE), epinephrine (E), or acetylcholine or intravenously with NE or E. Before, during, and after the infusions, simultaneous blood samples were taken without disturbing the animals. Infusion of NE into the LHA resulted in a decrease of plasma FFA and a simultaneous increase of insulin. NE infusion in the VMH elicited an increase of plasma FFA, plasma insulin, and blood glucose. E infusion into the LHA did not lead to a change of plasma FFA, whereas insulin and glucose showed an increase. E infusion into the VMH evoked increases of plasma FFA and insulin. Peripheral administration of NE led to a sharp increase of FFA, whereas plasma insulin and blood glucose did not change. E in the periphery elicited an augmentation of plasma FFA and blood glucose and a suppression of insulin during infusion. After termination of E infusion, plasma FFA and glucose levels decreased, whereas plasma insulin showed a sharp increase. It is concluded 1) that the effects produced by administration of NE and E are dependent on hypothalamic localization and local receptor population characteristics; 2) that there are striking differences regarding the effects on the investigated blood parameters between hypothalamically infused NE and E and peripherally infused NE and E; and 3) that the LHA and VMH are able to alter plasma FFA levels independently of blood glucose and insulin levels.

Відкриття української книгарні “Смолоскип”

The present medication in Parkinson’s disease (PD) is unable to stop or slow down the progression of the disease. Therefore pharmacological intervention at crucial steps in the neuronal cell death processes would be a better strategy. Cannabinoids are potent neuroprotective compounds in models of oxidative stress and excitotoxicity and offer potential protection in models of PD. Therefore the present study determines the neuroprotective effects of 9- tetrahydrocannabinol ( 9-THC) in the marmoset 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model on behavior and pathology. Twelve marmoset monkeys were treated with a total cumulative dose of 6 mg/kg MPTP in 9 days. Seven of these animals received simultaneously a daily oral dose of 9-THC (4 mg/kg) and five animals received simultaneously vehicle for 27 days. The parkinsonian symptoms were observed daily and locomotor activity and hand-eye coordination were tested once a week during the experimental period. Postmortem, dopamine levels in the striatum were analyzed and tyrosine hydroxylase immunohistochemistry was applied to determine viable dopaminergic neurons in the substantia nigra. 9-THC has no protective effects on any parameter. These negative results might be related to the severity of the cell death induction by MPTP in relation to the low dose of 9-THC used in this Parkinson model

Иммунно-нейроэндокринные взаимосвязи в развитии перименопаузальной патологии

Представлен современный патогенетический взгляд на происходящие в перименопаузальном периоде системные нарушения. Показано, что имунно-нейроэндокринный гомеостаз имеет определенные отличия в зависимости от клинической формы и степени тяжести перименопаузальных нарушений, что необходимо учитывать при проведении терапевтических мероприятий.Представлено сучасний патогенетичний погляд на системні порушення, що відбуваються в перименопаузальному періоді. Показано, що імунно-нейроендокринний гомеостаз має певні відмінності залежно від клінічної форми і ступеня тяжкості перименопаузальних порушень, що необхідно враховувати під час проведення терапевтичних заходів.A modern pathogenetic opinion about the systemic perimenopausal disorders is presented. It is shown that immunoneuroendocrine homeostatsis differs depending on the clinical form and degree of severity of perimenopausal disorders, which should be taken into consideration when taking therapeutic measures

Validation, comparison, and combination of algorithms for automatic detection of pulmonary nodules in computed tomography images: The LUNA16 challenge

Automatic detection of pulmonary nodules in thoracic computed tomography (CT) scans has been an active area of research for the last two decades. However, there have only been few studies that provide a comparative performance evaluation of different systems on a common database. We have therefore set up the LUNA16 challenge, an objective evaluation framework for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified. This paper describes the setup of LUNA16 and presents the results of the challenge so far. Moreover, the impact of combining individual systems on the detection performance was also investigated. It was observed that the leading solutions employed convolutional networks and used the provided set of nodule candidates. The combination of these solutions achieved an excellent sensitivity of over 95% at fewer than 1.0 false positives per scan. This highlights the potential of combining algorithms to improve the detection performance. Our observer study with four expert readers has shown that the best system detects nodules that were missed by expert readers who originally annotated the LIDC-IDRI data. We released this set of additional nodules for further development of CAD systems

Fetal and infant origins of asthma

Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life. Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children’s diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms. This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies

Concordant inter-laboratory derived concentrations of ceramides in human plasma reference materials via authentic standards

In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2%) and concordant (inter-laboratory CVs < 14%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals

Norepinephrine uptake by hypothalamic tissue from the rat related to feeding

Norepinephrine (NE) uptake by rat hypothalamus in vitro was studied in relation to food intake. Significant daily variations in NE uptake were observed in caudal hypothalamus from freely feeding rats. A maximal elevation occurred at the beginning of the night when food intake is also increasing to a maximum. NE uptake by caudal hypothalamus from relatively hungry rats previously adjusted to restricted feeding during the daytime was enhanced in afternoon and evening when compared with uptake by tissue from ad lib feeding animals. Determination of NE uptake by caudal hypothalamus from freely feeding individual rats and registration of individual meals taken by these rats revealed a relation between hypothalamic neuronal activity and the feeding pattern of the rat. A positive correlation was observed between NE uptake in vitro and feeding rate during a 2- to 4-hr interval. It also appeared that NE uptake by caudal hypothalamus is dependent on the time elapsed after the last meal. The data were evaluated in view of physiological studies concerning the onset of feeding and the hypothesis of hypothalamic adrenergic control of food intake