Preeclampsia is a long-term cardiovascular risk factor for the mother and possibly the offspring. Preeclampsia and cardiovascular diseases share common pathophysiological features, including endothelial dysfunction. We explored whether endothelial function, measured noninvasively, as well as circulating biomarkers reflecting lipid metabolism, angiogenesis, and inflammation, differed in paired mothers and offspring 5 to 8 years after delivery. Twenty-six mother and child pairs after pregnancies complicated by preeclampsia were compared with 17 mother and child pairs after uncomplicated pregnancies. In addition, we assessed whether concentrations of maternal circulating biomarkers at delivery predicted findings 5 to 8 years postpartum. We also included an assessment of early onset preeclampsia and specifically addressed the effects of small for gestational age. Endothelial function was significantly reduced in both mothers and children after preeclampsia when combined with a small-for-gestational-age infant compared with mothers and children after pregnancies without a small-for-gestational-age infant (mothers: P<0.001; children: P<0.05). Postpartum maternal soluble fms-like tyrosine kinase 1 (P=0.05) and high-sensitivity C-reactive protein (P=0.02) were elevated in the preeclampsia group compared with controls. High concentrations of these maternal biomarkers both at delivery and 5 to 8 years postpartum were also more frequent in preeclampsia compared with controls (P<0.05). The novelty of our study is the parallel finding of reduced endothelial function in mother and child pairs 5 to 8 years after small-for-gestational-age preeclamptic pregnancies, accompanied by increased inflammatory and antiangiogenic maternal biomarkers. This finding supports the concept of transgenerational risk of cardiovascular disease after preeclampsia.
The current study confirms that serum CgA is a sensitive marker for the detection of NE neoplasia. Elevated levels found in patients with adenocarcinoma may indicate NE differentiation in the tumour. CgA is a useful tool in the monitoring of enterochromaffin-like (ECL) hyperplasia secondary to treatment with acid secretion inhibitors or atrophic gastritis.
ABSTRACT.Purpose: The maximum post-mortem time limit for obtaining donor corneas varies between eye banks. It is not known for how long a time the epithelial cells survive post-mortem, nor is it known if donor corneas with extended postmortem time are able to regenerate the epithelium. Therefore, we wanted to examine the epithelium in donor corneas for regenerative ability during storage in an eye bank organ culture system. Methods: Twenty-four paired donor corneas with post-mortem time from 28 to 163 hr were obtained. One cornea of a pair was fixed immediately to serve as a control, and the second was cultured in eye bank medium at 32°C for 3 days. Examination of the specimens was performed with light and scanning electron microscopy. Immunohistochemical staining methods with antibodies against K 3, K 19, vimentin and p63 were used to further characterize the cells. Results: The control corneas showed decreasing amounts of epithelial cells with increasing post-mortem time. All the cultured corneas demonstrated rapid regeneration of the epithelium. After 3 days in organ culture, 10 of 12 donor corneas were covered with epithelium. Conclusion: Even up to 7 days post-mortem, viable cells reside in the corneal epithelium. The study demonstrates the hardiness and enormous regenerative potential of peripheral corneal cells. Donor corneas processed in an eye bank organ culture storage system will obtain an intact epithelial layer within a few days.
ABSTRACT.Purpose: To compare the histology, phenotype, ultrastructure and barrier function of cultured limbal epithelial cells using two explant culture protocols. Methods: Epithelial cells were cultured for 16 days from limbal explants, positioned with either the stromal side (stromal group) or the epithelial side (epithelial group) on intact amniotic membranes. The cultured epithelium (n = 56) was examined using light microscopy, immunohistochemistry for K3, Cx43, ABCG2 and p63 expression, Western blot analysis of DNp63a, transmission electron microscopy, a horseradish peroxidase (HRP) permeability assay and scanning electron microscopy.Results: The epithelial group demonstrated a significantly higher expression of p63-positive cells (85.7 ± 4.2%) than the stromal group (75.3 ± 8.9%), and Western blots showed a stronger band of DNp63a. K3 and ABCG2 were not detected in either group, whereas Cx43 displayed moderate immunostaining in the suprabasal layer. The number of cell layers, the desmosome number and the undulation length in the epithelial group were not significantly different from those in the stromal group. In both groups, HRP accumulated on the apical surface of the superficial cells, and scanning electron microscopy demonstrated tightly apposed superficial cells. Conclusions: Our findings indicate that limbal explants positioned epithelial side down may give rise to cultured epithelia with higher expression of p63 and DNp63a.
The study showed survival of the corneal endothelium up to 7 days postmortem, and accordingly, the potential clinical use of donor corneas with extended postmortem time. Our results furthermore suggest that repair of the endothelium in donor corneas during organ culture storage occurs also by proliferation and not only by migration and enlargement of existing cells. If we uncover the mechanisms regulating cell proliferation in corneal endothelium, it should be possible to develop better storage methods of corneal transplants to improve quality and supply.
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Purpose: Donor corneas are processed in eye banks and used for transplantation as a standard routine. The maximum time limit post‐mortem for harvesting donor tissue varies greatly between eye banks. This study aimed to examine the corneal epithelium for structural changes post‐mortem.
Methods: A total of 51 corneas harvested between 14 and 163 hours post‐mortem were examined using scanning electron and light microscopy.
Results: Cell loss occurred through desquamation of flat superficial cells during the first days. In corneas with a post‐mortem time of more than 2−3 days, large superficial cell sheets and deeper cells detached, starting centrally. Deep peripheral cells remained. The loss of the superficial cells revealed the 3‐dimensional structure of the epithelium and the membrane characteristics of deeper cells.
Conclusion: The longer the time post‐mortem, the greater the epithelial cell loss. However, a rim of peripheral cells remained, even after 7 days. The superficial cell layer showed signs of strong lateral attachment and broke up in a sheet‐like fashion. The intercellular adhesion between deeper cells and adhesion between the basal cells and the basement membrane appeared to be weak post‐mortem. The cell membrane structures of the remaining cells were surprisingly well retained. The clinical implication of the study is discussed.
Background and aims: Preeclampsia and diabetic pregnancies share many pathophysiological features suggested to influence epigenetic changes during foetal life with importance for childhood development and later metabolic and cardiovascular diseases. Our objective was to study early myocardial affections in offsprings after these pregnancy complications.
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