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- Korchynska, Solomiia, et al.
(författare)
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Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants
- 2020
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Ingår i: EMBO Journal. - : EMBO. - 1460-2075 .- 0261-4189. ; 39:1
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Tidskriftsartikel (refereegranskat)abstract
- Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly. Exacerbated dopamine signaling is particularly considered as a key determinant of psychostimulant action. Much less is known about possible adverse effects of these drugs on peripheral organs, and if in utero exposure induces lifelong pathologies. Here, we addressed this question by combining human RNA-seq data with cellular and mouse models of neuroendocrine development. We show that episodic maternal exposure to psychostimulants during pregnancy coincident with the intrauterine specification of pancreatic β cells permanently impairs their ability of insulin production, leading to glucose intolerance in adult female but not male offspring. We link psychostimulant action specifically to serotonin signaling and implicate the sex-specific epigenetic reprogramming of serotonin-related gene regulatory networks upstream from the transcription factor Pet1/Fev as determinants of reduced insulin production.
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| 2. |
- Pifl, Markus, et al.
(författare)
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Histomorphometric analysis of the palatal soft tissue as donor region for retrieval of connective tissue grafts
- 2014
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives The soft tissue of the palate is the most frequently used donor side for connective tissue grafts. Various techniques have been described to harvest the connective tissue in anterior and posterior regions of the palate (Hürzeler 1999, Jung 2008, Zucchelli 2010). The present study assessed the histological composition of the soft tissue of the palate in the premolar and tuberosity region and compared the histological composition of connective tissue grafts harvested by two different techniques. Methods Tissue samples of the palatal soft tissue of 10 fresh human dentate cadaver heads were harvested in the premolar and tuberosity region. After histological processing, a histomorphometric analysis on the ratio between epithelium, connective tissue, fatty/glandular tissue, and vascular tissue was performed. Height and composition of the total palatal tissue and of digitally marked grafts (two different harvesting techniques: split-flap- and de-epithelialization-technique) were assessed in both regions (premolar and tuberosity) in an area close and more distant from the teeth (Figure 1). Results The height measurements of the palatal soft tissue ranged from 2.4 to 6.9mm. The main parameters (ratio of connective tissue and fatty/glandular tissue) presented no significant difference between the various regions (close and distant areas in the premolar and tuberosity region; p>0.145; Table 1). But significant differences were detected for the histological compositions of the connective tissue grafts (Table 2); the tissue gained by de-epithelialization in the tuberosity region contained a significantly higher amount of connective tissue, than the tissue gained by split-flap-technique in the premolar region (73.3 vs. 56.5%; p=0.041; Figure 2). Altogether, both, height measurements and composition of the palatal tissue, presented a high inter-individual variability (e.g., percentage of fatty/glandular tissue ranged from 0.04 to 73.8%; Figure 3). Comparison between genders revealed significantly higher values of connective tissue in the premolar region of males (p=0.045); all other parameters presented no relevant gender differences (p>0.077). Conclusions Thus far, the connective tissue harvested in the tuberosity region, which is most often done by de-epithelialization to prevent injury to the greater palatine artery (Figure 1), was clinically described to be denser and more firm compared to the tissue gained in the premolar region (most often by split-flap-technique) (Zuhr 2014). The present study is, to the best of our knowledge, the first to prove this clinical assumption with a histomorphometric analysis. Topic of future clinical trials will be to assess, whether the outcome of root coverage procedures is influenced by the histological composition of the graft (more or less fatty).
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