Offspring of hypertensive pregnancies are at increased risk of developing hypertension in adulthood. In the neonatal period they display endothelial cell dysfunction and altered microvascular development. MicroRNAs, as important endothelial cellular regulators, may play a role in this early endothelial dysfunction. Therefore we identified differential microRNA patterns in endothelial cells from offspring of hypertensive pregnancies and determined their role in postnatal vascular cell function. Studies were performed on human umbilical vein endothelial cell (HUVECs) samples from 57 pregnancies. Unbiased RNA-sequencing identified 30 endothelial-related microRNAs differentially expressed in HUVECs from hypertensive compared to normotensive pregnancies. Quantitative reverse transcription PCR (RT-qPCR) confirmed a significant higher expression level of the top candidate, miR-146a. Combined miR-146a targeted gene expression and pathway analysis revealed significant alterations in genes involved in inflammation, angiogenesis and immune response in the same HUVECs. Elevated miR-146a expression level at birth identified cells with reduced ability for in vitro vascular tube formation, which was rescued by miR-146a inhibition. In contrast, miR-146a overexpression significantly reduced vascular tube formation in HUVECs from normotensive pregnancies. Finally, we confirmed that mir146a levels at birth predicted in vivo microvascular development during the first three postnatal months. Offspring of hypertensive pregnancy have a distinct endothelial regulatory microRNA profile at birth, which is related to altered endothelial cell behaviour, and predicts patterns of microvascular development during the first three months of life. Modification of this microRNA profile in vitro can restore impaired vascular cell function.
The only advantage of the Davis pipette is that patients can take their own sample without the need to attend a clinic or to see a doctor; it might therefore be possible to reach a larger proportion of the population at risk. However, the low rate of detection would necessitate repeated screenings of each patient at fairly short time-intervals, and although the initial response might be good, it could prove difficult to persuade women to take repeated samples, especially in view of the complaints from the clinics participating in this survey. Like Macgregor and her colleagues, we think that the cytopipette is not an appropriate instrument for urban-community-screening programmes.
ConclusionsOur results leave us in no doubt that when a cervical cytology specimen is taken by a doctor the Ayre smear is a more effective method than the Davis cytopipette in the detection of malignancy. The Davis method has been extensively used in Denmark (Bredahl et al., 1965) al., 1962, 1963) and subsequently both have been found useful in patients with rheumatoid arthritis (Coodley, 1963;Young, 1963
The response to bumetanide and furosemide administered orally and intravenously was compared in normal subjects. Doses of bumetanide were 0.5 and 1 mg intravenously and 0.5, 1 and 2 mg orally. Doses of furosemide were 20 and 40 mg intravenously and 20, 40, and 80 mg orally. After intravenous doses of both drugs, peak natriuresis occurred during the first collection period of 30 minutes and the response returned to baseline by 3.5 hours. After oral dosing, peak effect occurred at 75 minutes and returned to baseline within 4 hours. Cumulative response was assessed for volume, sodium, potassium, and chloride excretion. The response did not differ substantially between drugs. On a milligram basis, bumetanide was approximately 50 times as potent as furosemide. For both drugs, the intravenous dose was approximately three times as potent as the oral preparation. The time course of response shows that the curves are virtually superimposable. The diuretic effect was short-lived for both diuretics. The urine volume and sodium and chloride excretion were parallel. The sodium/potassium ratio was calculated as follows: for every 200 mEq sodium excreted in 4 hours, bumetanide caused about 35 mEq and furosemide caused about 50 mEq potassium to be eliminated. Even if statistically significant, this difference does not appear to be clinically remarkable. If bumetanide offers therapeutic advantages in this regard, studies in patients with various disease states would have to be performed.
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