Effects of interleukin-1 beta on thyrotropin secretion and thyroid hormone uptake in cultured rat anterior pituitary cells

The effects of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) on basal and TRH-induced TSH release, and the effects of IL-1 beta on the uptake of [125I]T3 and [125I]T4 and on nuclear binding of [125I]T3 were examined. Furthermore, the release of other anterior pituitary hormones in the presence of IL-1 beta was measured. Anterior pituitary cells from male Wistar rats were cultured for 3 days in medium containing 10% FCS. Incubation were performed at 37 C in medium with 0.5% BSA for measurement of [125I]T3 uptake and with 0.1% BSA for measurement of [125I]T4 uptake. Exposure to IL-1 beta (1 pM-1 nM) or TNF alpha (100 pM) for 2-4 h resulted in a significant decline in TSH release, which was almost 50% (P < 0.05) for 1 nM IL-1 beta and 24% (P < 0.05) for 100 pM TNF alpha. Measurement of other anterior pituitary hormones (FSH, LH, PRL, and ACTH) in the same incubation medium showed that IL-1 beta did not alter their release. When the effects of IL-1 beta (1 pM-1 nM) and TNF alpha (100 pM) on TRH-induced TSH release were measured in short term experiments, the inhibitory effects had disappeared. The addition of 1-100 nM octreotide, a somatostatin analog, resulted in a decrease in TRH-induced TSH release up to 33% of the control value (P < 0.05). Exposure to dexamethasone (1 nM to 1 microM) affected basal and TRH-induced TSH release similar to the effect of IL-1 beta. The 15-min uptake of [125I]T3 and [125I]T4, expressed as femtomoles per pM free hormone, was not affected by the presence of IL-1 beta (1-100 pM). When IL-1 beta (100 pM) was present during 3 days of culture, TSH release was reduced to 88 +/- 2% of the control value (P < 0.05). This effect was not associated with an altered [125I]T3 uptake (15 min to 4 h) or with any change in nuclear T3 binding. We conclude that 1) IL-1 beta decreases TSH release by a direct action on the pituitary; 2) this effect is not due to elevated thyroid hormone uptake or increase T3 nuclear occupancy; 3) IL-1 beta does not affect TRH-induced TSH release or the release of other anterior pituitary hormones; and 4) TNF alpha affects basal and TRH-induced TSH release in the same way as IL-1 beta

ECG-Gated Three-dimensional Intravascular Ultrasound

Background Automated systems for the quantitative analysis of three-dimensional (3D) sets of intravascular ultrasound (IVUS) images have been developed to reduce the time required to perform volumetric analyses; however, 3D image reconstruction by these nongated systems is frequently hampered by cyclic artifacts. Methods and Results We used an ECG-gated 3D IVUS image acquisition workstation and a dedicated pullback device in atherosclerotic coronary segments of 30 patients to evaluate (1) the feasibility of this approach of image acquisition, (2) the reproducibility of an automated contour detection algorithm in measuring lumen, external elastic membrane, and plaque+media cross-sectional areas (CSAs) and volumes and the cross-sectional and volumetric plaque+media burden, and (3) the agreement between the automated area measurements and the results of manual tracing. The gated image acquisition took 3.9±1.5 minutes. The length of the segments analyzed was 9.6 to 40.0 mm, with 2.3±1.5 side branches per segment. The minimum lumen CSA measured 6.4±1.7 mm2, and the maximum and average CSA plaque+media burden measured 60.5±10.2% and 46.5±9.9%, respectively. The automated contour-detection required 34.3±7.3 minutes per segment. The differences between these measurements and manual tracing did not exceed 1.6% (SD<6.8%). Intraobserver and interobserver differences in area measurements (n=3421; r=.97 to.99) were <1.6% (SD<7.2%); intraobserver and interobserver differences in volumetric measurements (n=30; r=.99) were <0.4% (SD<3.2%). Conclusions ECG-gated acquisition of 3D IVUS image sets is feasible and permits the application of automated contour detection to provide reproducible measurements of the lumen and atherosclerotic plaque CSA and volume in a relatively short analysis time

Atherosclerotic coronary lesions with inadequate compensatory enlargement have smaller plaque and vessel volumes: observations with three dimensional intravascular ultrasound in vivo.

OBJECTIVE: To compare vessel, lumen, and plaque volumes in atherosclerotic coronary lesions with inadequate compensatory enlargement versus lesions with adequate compensatory enlargement. DESIGN: 35 angiographically significant coronary lesions were examined by intravascular ultrasound (IVUS) during motorised transducer pullback. Segments 20 mm in length were analysed using a validated automated three dimensional analysis system. IVUS was used to classify les

Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: a pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients

Background: Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.Methods: Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).Results: A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.Conclusion: In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and pa-tients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in pa-tients using clopidogrel.(c) 2021 Published by Elsevier B.V.Cardiolog

Simpson's rule for the volumetric ultrasound assessment of atherosclerotic coronary arteries: a study with ECG-gated three-dimensional intravascular ultrasound.

BACKGROUND: Volumetric intravascular ultrasound (IVUS) assessment provides complementary information on atherosclerotic plaques. The volumes can be calculated by applying Simpson's rule to cross-sectional area data of multiple IVUS images, acquired with a fixed sample spacing, which is the distance (along the vessel's axis) between two images. OBJECTIVE: To evaluate the effect of different sample spacings on the results of volumetric IVUS measurements. METHODS: A stepwise electrocardiographically gated IVUS image-acquisition and automated three-dimensional analysis approach was applied to 26 patients. Twenty-eight coronary segments with mild-to-moderate coronary atherosclerosis were examined. Volumetric measurements of five images per mm (i.e. sample spacing 0.2 mm), representing a complete scanning of the coronary segment, were considered the optimal standard, against which volumetric measurements of three, one, and one-half images per mm (i.e. larger sample spacings) were compared. RESULTS: The lumen, total vessel, an

Successful directional atherectomy of de novo coronary lesions assessed with three-dimensional intravascular ultrasound and angiographic follow-up.

Recent histopathologic and intravascular ultrasound (IVUS) data indicate that inadequate compensatory enlargement of atherosclerotic lesions contributes to the development of significant arterial stenoses. Such lesions may conta