4 research outputs found
Effects of thyroid status and thyrostatic drugs on hepatic glucuronidation of lodothyronines and other substrates in rats - Induction of phenol UDP-glucuronyltransferase by methimazole
Glucuronidation of iodothyronines in rat liver is catalyzed by at least three UDP-glucuronyltransferases (UGTs): bilirubin UGT, phenol UGT, and androsterone UGT. Bilirubin and phenol UGT activities are regulated by thyroid hormone, but the effect of thyroid status on hepatic glucuronidation of iodothyronines is unknown. We examined the effects of hypothyroidism induced by treatment of rats with propylthiouracil (PTU) or methimazole (MMI) or by thyroidectomy as well as the effects of T4-induced hyperthyroidism on the hepatic UGT activities for T4, T3, bilirubin, p-nitrophenol (PNP), and androsterone. Bilirubin UGT activity was increased in MMI- or PTU-induced hypothyroid and thyroidectomized rats, and decreased in hyperthyroid animals. T4 and, to a lesser extent, T3 UGT activities were increased in MMI- or PTU-induced hypothyroid rats, and T4 but not T3 glucuronidation also showed a significant increase in thyroidectomized rats. T4 but not T3 UGT activity was slightly decreased in hyperthyroid rats. While PNP UGT activity was decreased in thyroidectomized rats and increased in hyperthyroid animals, it was also markedly increased by MMI and slightly increased by PTU-induced hypothyroidism. In T4-substituted rats, MMI did not affect T4, T3, bilirubin and androsterone UGT activities but again strongly induced PNP UGT activity, indicating that this represented a direct induction of PNP UGT by the drug independent of its thyrostatic action. Androsterone UGT activity was hardly affected by thyroid status. Our results suggest a modest, negative control of the hepatic glucuronidation of thyroid hormone by thyroid status, which may be mediated by changes in bilirubin UGT activity. To our knowledge, this is the first report of the marked induction of a hepatic enzyme by MMI, which is not mediated by its thyroid hormone-lowering effect
Outcome from balloon induced coronary artery dissection after intracoronary beta radiation
OBJECTIVE: To evaluate the healing of balloon induced coronary artery
dissection in individuals who have received beta radiation treatment and
to propose a new intravascular ultrasound (IVUS) dissection score to
facilitate the comparison of dissection through time. DESIGN:
Retrospective study. SETTING: Tertiary referral centre. PATIENTS: 31
patients with stable angina pectoris, enrolled in the beta energy
restenosis trial (BERT-1.5), were included. After excluding those who
underwent stent implantation, the evaluable population was 22 patients.
INTERVENTIONS: Balloon angioplasty and intracoronary radiation followed by
quantitative coronary angiography (QCA) and IVUS. Repeat QCA and IVUS were
performed at six month follow up. MAIN OUTCOME MEASURES: QCA and IVUS
evidence of healing of dissection. Dissection classification for
angiography was by the National Heart Lung Blood Institute scale. IVUS
proven dissection was defined as partial or complete. The following IVUS
defined characteristics of dissection were described in the affected
coronary segments: length, depth, arc circumference, presence of flap, and
dissection score. Dissection was defined as healed when all features of
dissection had resolved. The calculated dose of radiation received by the
dissected area in those with healed versus non-healed dissection was also
compared. RESULTS: Angiography (type A = 5, B = 7, C = 4) and IVUS proven
(partial = 12, complete = 4) dissections were seen in 16 patients
following intervention. At six month follow up, six and eight unhealed
dissections were seen by angiography (A = 2, B = 4) and IVUS (partial = 7,
complete = 1), respectively. The mean IVUS dissection score was 5.2 (range
3-8) following the procedure, and 4.6 (range 3-7) at follow up. No
correlation was found between the dose prescribed in the treated area and
the presence of unhealed disse
Geometric vascular remodeling after balloon angioplasty and beta-radiation therapy: A three-dimensional intravascular ultrasound study
BACKGROUND: Endovascular radiation appears to inhibit intimal thickening
after overstretching balloon injury in animal models. The effect of
brachytherapy on vascular remodeling is unknown. The aim of the study was
to determine the evolution of coronary vessel dimensions after
intracoronary irradiation after successful balloon angioplasty in humans.
METHODS AND RESULTS: Twenty-one consecutive patients treated with balloon
angioplasty and beta-radiation according to the Beta Energy Restenosis
Trial-1.5 were included in the study. Volumetric assessment of the
irradiated segment and both edges was performed after brachytherapy and at
6-month follow-up. Intravascular ultrasound images were acquired by means
of ECG-triggered pullback, and 3-D reconstruction was performed by
automated edge detection, allowing the calculation of lumen, plaque, and
external elastic membrane (EEM) volumes. In the irradiated segments, mean
EEM and plaque volumes increased significantly (451+/-128 to 490.9+/-159
mm(3) and 201.2+/-59 to 241.7+/-74 mm(3); P=0.01 and P=0.001,
respectively), whereas luminal volume remained unchanged (250.8+/-91 to
249.2+/-102 mm(3); P=NS). The edges demonstrated an increase in mean
plaque volume (26.8+/-12 to 32. 6+/-10 mm(3), P=0.0001) and no net change
in mean EEM volume (71. 4+/-24 to 70.9+/-24 mm(3), P=NS), resulting in a
decrease in mean luminal volume (44.6+/-16 to 38.3+/-16 mm(3), P=0.01).
CONCLUSIONS: A different pattern of remodeling is observed in coronary
segments treated with beta-radiation after successful balloon angioplasty.
In the irradiated segments, the adaptive increase of EEM volume appears to
be the major contributor to the luminal volume at follow-up. Conversely,
both edges showed an increase in plaque volume without a net change in EEM
volume
beta-Particle-emitting radioactive stent implantation. A safety and feasibility study
BACKGROUND: This study represents the Heart Center Rotterdam's
contribution to the Isostents for Restenosis Intervention Study, a
nonrandomized multicenter trial evaluating the safety and feasibility of
the radioactive Isostent in patients with single coronary artery disease.
Restenosis after stent implantation is primarily caused by neointimal
hyperplasia. In animal studies, beta-particle-emitting radioactive stents
decrease neointimal hyperplasia by inhibiting smooth muscle cell
proliferation. METHODS AND RESULTS: The radioisotope (32)P, a
beta-particle emitter with a half-life of 14.3 days, was directly embedded
into the Isostent. The calculated range of radioactivity was 0.75 to 1.5
microCi. Quantitative coronary angiography measurements were performed
before and after the procedure and at 6-month follow-up. A total of 31
radioactive stents were used in 26 patients; 30 (97%) were successfully
implanted, and 1 was embolized. Treated lesions were in the left anterior
descending coronary artery (n=12), the right coronary artery (n=8), or the
left circumflex coronary artery (n=6). Five patients received additional,
nonradioactive stents. Treated lesion lengths were 13+/-4 mm, with a
reference diameter of 2.93+/-0. 47 mm. Minimum lumen diameter increased
from 0.87+/-0.28 mm preprocedure to 2.84+/-0.35 mm postprocedure. No
in-hospital adverse cardiac events occurred. All patients received aspirin
indefinitely and ticlopidine for 4 weeks. Twenty-three patients (88%)
returned for 6-month angiographic follow-up; 17% of them had in-stent
restenosis, and 13% had repeat revascularization. No restenosis was
observed at the stent edges. Minimum lumen diameter at follow-up averaged
1.85+/-0.69 mm, which resulted in a late loss of 0.99+/-0. 59 mm and a
late loss index of 0.53+/-0.35. No other major cardiac events occurred
during the 6-month follow-up. CONCLUSIONS: The use of radioactive stents
with an activity of 0.75 to 1.5 microCi is safe and feasible