Aliment Pharmacol Ther 31, 634–639
Summary
Background Endoscopic balloon dilation has been shown to be an alternative to surgery in the treatment of Crohn’s symptomatic strictures.
Aim To analyse ...the impact of the type of the strictures –de novo or anastomotic – their location and their length on the outcome of endoscopic balloon dilation.
Methods Between December 1999 and June 2008, 55 patients underwent 93 balloon dilations for 74 symptomatic strictures. One stricture was located in the duodenum, 39 strictures were in the terminal ileum, 17 at the ileocoecal anastomosis after a preceding resection and 17 in the colon.
Results Endoscopic treatment was successful in 76% of the patients during an observation period of 44 (1–103) months. Of the patients, 24% required surgery. All patients who underwent surgery had de novo strictures in the terminal ileum. These strictures were significantly longer compared with the ileal strictures that responded to endoscopic treatment 7.5 (1–25) cm vs. 2.5 (1–25) cm; P = 0.006.
Conclusions The long‐term success of endoscopic balloon dilation depends on the type of the strictures, their location and their length. Failure of endoscopic treatment was observed only in long‐segment strictures in the terminal ileum.
Iodine induced thyroid involution is caused by apoptosis rather than necrosis. This effect of iodide on apoptosis of thyroid epithelial cells may be not a direct one but mediated by iodinated ...derivatives i.e. of polyunsaturated fatty acids, especially of iodolactones, which have previously shown to inhibit thyroid cell proliferation. We studied the influence on apoptosis of iodide (2 microM and 20 microM) and iodolactone (0.05 microM and 0.5 microM), with and without TSH (1 mU/ml), using a well characterized ex vivo- culture system of intact porcine thyroid follicles in three-dimensional culture. Apoptosis and necrosis was evaluated by electron-microscopy. Stimulation with 2 and 20 microM iodide rapidly induced a rate of apoptosis (4 - 6 %) comparable to about 40-fold lower doses of delta-iodolactone (0.05 microM and 0.5 microM). Addition of TSH (1 mU/ml) caused a slight but not significant further increase of the incidence of apoptotic cells. The rate of necrotic thyroid epithelial cells (1 - 2 %) was similar in all experiments. As delta-iodolactone in very low concentrations--comparable to iodide in higher concentrations--not only inhibits growth but also induces apoptosis, it has to be supposed that the effect of iodide is mediated by this iodinated compound. However, further experiments are necessary to confirm this hypothesis. In addition it could be demonstrated, that apoptosis is a very rapid and limited process in intact follicles. This also may explain, why iodine supplementation even in high doses does not lead to thyroid atrophy but only normalisation of thyroid size. These results confirm that apoptosis is an important regulated and limited mechanism in goiter involution.
Increasing evidence has accumulated for rapid nongenomic steroid actions in various cell systems and, more recently, for rapid aldosterone effects on the Na(+)-H+ antiport in human mononuclear ...leukocytes. The aim of the present study was to demonstrate a rapid, nongenomic aldosterone action in rat vascular smooth muscle cells as a key effector cell in cardiovascular regulation. Basal 22Na+ influx in quiescent vascular smooth muscle cells was 22.1 +/- 1.9 nmol/mg protein per minute (mean +/- SEM, n = 9). Aldosterone (1 nmol/L) stimulated influx to 28.6 +/- 1.5 nmol/mg protein per minute after 4 minutes (n = 9, P < .05), with a half-maximal effect between 0.1 and 0.5 nmol/L; the effects were inhibited by ethylisopropylamiloride, the specific inhibitor of the Na(+)-H+ exchanger, demonstrating the involvement of this transport system in rapid effects of aldosterone. Hydrocortisone (1 mumol/L) was ineffective, and fludrocortisone and deoxycorticosterone increased influx with half-maximal effects at approximately 0.5 nmol/L. Canrenone, a classic antagonist of aldosterone action, did not inhibit stimulation by aldosterone at a 1000-fold excess concentration. Aldosterone significantly stimulated intracellular inositol 1,4,5-trisphosphate levels (P < .05) after 30 seconds; the inhibitors of phospholipase C, neomycin and U-73122, inhibited aldosterone-stimulated Na+ influx and increase of intracellular inositol 1,4,5-trisphosphate. The rapid stimulation of sodium transport in vascular smooth muscle cells and the pharmacological characteristics of this effect are clearly incompatible with the classic, genomic pathway of steroid action and represent further evidence for nongenomic effects of aldosterone.
There is evidence that iodoarachidonates are mediators of iodide in thyroid autoregulation, however, their occurrence in vivo has not yet been demonstrated. We therefore tried to identify ...delta-iodolactone (5-Hydroxy-6-iodo-8,11,14-eicosatrienoic delta-lactone, IL-delta) in thyroid tissue from a patient with Graves' disease treated with high doses of iodide. Lipids were extracted from thyroid tissue, purified by reversed phase chromatography and analyzed by gas chromatography--tandem mass spectrometry (GC-MSMS). The retention time in gas chromatography and fragmentation pattern in tandem mass spectrometry were determined with biochemically synthesized non-deuterated and deuterated IL-delta. According to retention time (13.44 min) and specific fragments (m/z 303, m/z 259) the occurrence of IL-delta could be demonstrated in the extract of iodide treated goiter. In vitro, potassium iodide (40 microM) as well as IL-delta (1.0 microM) significantly inhibited the proliferation of human thyroid follicular cells induced by phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate). These results demonstrate for the first time that Il-delta is present in iodide treated human thyroid. As cell proliferation is under negative control of IL-delta, a crucial role in thyroid involution following iodide treatment may be possible.
For thyroid cells in culture DNA fragmentation and morphological changes related to apoptosis were first described in dog thyroid cells after deprivation of serum, epidermal growth factor or ...thyrotropin. With intact porcine thyroid follicles in three-dimensional culture, the effect of deprivation of growth factors and of incubation with transforming growth factor beta1 (TGF-beta1), epidermal growth factor (EGF), thyrotropin (TSH) or insulin-like growth factor 1 (IGF-1) on the incidence of apoptosis was studied. Thyroid follicles were embedded in growth factor-depleted Matrigel and cultured in serum-free medium with or without growth factors for 7 days followed by incubation for 4, 24 and 72 h with TGF-beta1 (2 or 5 ng/mL). The percentage of apoptotic cells was determined by direct counting in electron-microscopy. Approximately 1% of apoptotic bodies could be detected in unstimulated follicles. This was unchanged in the presence of TSH (1 mU/mL) or IGF (10 ng/mL) but significantly increased up to 3.99 +/- 1.24% with 2 ng/mL of EGF. After incubation with TGF-beta apoptosis increased dose-dependently to 4.05 +/- 0.67% with 2 ng/mL TGF-beta1 and 5.16 +/- 1.75% with 5 ng/mL TGF-beta1. The incidence of necrotic cells remained constant at about 1 to 2%. Preincubation of follicles with 2 ng/mL of EGF followed by incubation with 5 ng/mL TGF-beta1 increased the rate of apoptic bodies up to 13.19 +/- 1.9%. We conclude that growth factor depletion in thyroid follicles in three-dimensional culture does not lead to apoptosis. TGF-beta1, however, induces apoptosis even in quiescent thyroid follicular cells and is significantly more pronounced in growing thyroid cells. EGF, which is a dedifferentiating growth factor for thyroid cells, also induces apoptosis. As EGF enhances TGF-beta1 mRNA and protein in thyroid follicular cells, the induction of apoptosis by EGF might also be due to TGF-beta1
We compared the iodine excretion and thyroid volumes in young students with or without continuous use of iodized salt in household. Students from five different Universities in Bavaria were evaluated ...on a voluntary basis. Exclusion criteria were age above 35 years, known thyroid illness except simple goiter, application of x-ray contrast medium within the last 6 months or other known exposure to high doses of iodine. The participants answered a questionnaire indicating permanent utilization of iodized salt for more than one year during all their meals, the intake of iodide tablets and eating in student cafeterias, offering meals that are prepared with iodized salt. Morning spot urine was drawn from each participant to measure creatinine correlated iodide excretion and thyroid volume was measured by ultrasound. In this study, 932 students could be included, mean age was 24 years, 501 females, 431 males. Chronic users of iodized salt were 75.9% (80.4% females, 70.5% males), 1.7% were on iodide tablets (200 micrograms/day) and 2.6% were on TSH suppressive therapy with thyroid hormones. The mean iodide excretion in chronic iodized salt users was 72.0 (+/- 68.7) micrograms/g creatinine compared to non-users 66.0 (+/- 65.4) micrograms/g creatinine (p < 0.003). Those students who were on iodide tablets had a mean iodide excretion of 130.0 +/- 72.0 micrograms/g creatinine. Mean thyroid volume was 14.1 (4.4-44.1) ml in females and 17.1 (6.6-64.4) ml in males, solid thyroid nodules were detected in 5.9% and thyroid cysts in 2.7% of the participants without any difference between iodized salt users or non-users.
Immunoreactive basic fibroblast growth factor (bFGF) could be isolated from the cytosol preparation of isolated porcine thyroid follicles as well as in the conditioned medium from thyroid follicles ...in suspension culture. A double band with 16,500 and 15,500 D was detected on sodium dodecyl sulfate polyacrylamide gel electrophoresis. In dot blot and western blot the isolated peptide was immunoreactive with a specific anti-bovine bFGF antibody. For further biochemical characterization, bFGF was isolated from entire porcine thyroid glands by ammonium sulfate precipitation, cation exchange chromatography and heparin affinity chromatography. The material obtained from all three origins was identical concerning affinity to heparin and immunoreactivity with the specific anti-bovine bFGF antibody and induced neovascularization in the chorioallantois membranes of chick embryos. Amino acid sequence analysis of the 16-amino-terminal amino acids of the isolated bFGF was in accordance with the established complete 146-amino-acid bFGF molecule except that glycine in position 10 is replaced by phenylalanine. An additionally identified minor peptide presumably is an amino-terminal-truncated form of bFGF, missing the first 15 amino acids. We conclude that the physiological significance of bFGF released by thyroid cells may be the regulation of angiogenesis during thyroid development and goiter growth.
Iodolactone (6-iodo-8,11,14-eicosatrienoic-delta-lactone), an iodinated derivative of arachidonic acid, was found to be synthesized in rat thyroid slices; however, the physiological role of this ...compound is still unknown. We tried to detect iodolactone in isolated porcine thyroid follicles and investigated the effects of in vitro synthesized iodolactone on epidermal growth factor-induced thyroid cell proliferation and TSH-induced cAMP formation. In vitro synthesis of iodolactone was performed with lactoperoxidase-catalyzed iodination of arachidonic acid in the presence of trace amounts of 125I- and 3Harachidonic acid. After purification by silica gel chromatography, HPLC of the reaction products revealed one main peak containing trace amounts of both 125I- and 3Harachidonic acid. With gas chromatography-mass spectrometry (GC-MS) a molecular mass of 391 m/z, corresponding to the derivatization product of iodolactone, was found. An ethanol-chloroform extract of isolated thyroid follicles preincubated with KI (10 microM) and arachidonic acid (1 microM) revealed peaks in HPLC and GC comparable with those of in vitro synthesized iodolactone. This indicates the ability of thyroid follicles to form iodolactone. Iodolactone (0.1-1.0 microM) dose-dependently inhibited epidermal growth factor-induced thyroid cell growth. This growth-inhibiting effect of iodolactone was 50-fold more pronounced than the inhibitory effect of KI (4 X 10(-5) microM) on thyroid cell proliferation. In contrast to the effect of iodide, the inhibitory effect of iodolactone on thyroid cell growth could not be abolished by methimazole (1 mM). Basal as well as TSH (0.5 U/liter)-induced cAMP formation were not changed by iodolactone. These experiments suggest a physiological role of iodolactone as a mediator of the known inhibitory effect of iodide on thyroid growth.
Interleukin-1 beta (IL-1 beta) is known to be involved in autoimmune thyroiditis. Since the results of different in vitro-studies on the effect of IL-1 on thyrocytes are controversial, our aim was to ...investigate the existence of specific binding sites for IL-1 beta and its influence on specific functions and growth of isolated porcine thyroid follicles ex vivo with a preserved iodide metabolism. For binding studies isolated thyroid follicles were incubated with 125I-IL-1 beta (213.5 nCi/ml) and with increasing concentrations of unlabelled IL-1 beta (0.06-11.5 nmol/l) for 24 h at 4 degrees C. The dissociation constant Kd was 0.85 x 10(-10) mol/l and about 800 binding sites per cell were calculated. IL-1 beta (10 U/ml) decreased basal and TSH-stimulated iodide uptake and organification after an incubation time of 45 min to 6 h without any influence on cAMP-formation. In addition, after 40 h of incubation IL-1 beta dose-dependently increased T3-secretion, followed by a decrease during simultaneous TSH-stimulation, whereas there was no effect on T4-secretion. In contrast to these functional effects IL-1 beta showed no influence on the growth of thyroid follicles, so that the cytokine cannot be made responsible for goiter growth in thyroid diseases by directly influencing thyroxytes.
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