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December 2002

Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys.

Soy protein, long recognized as having cardiovascular benefits, is a rich source of phytoestrogens (isoflavones). To distinguish the relative contributions of the protein moiety versus the alcohol-extractable phytoestrogens for cardiovascular protection, we studied young male cynomolgus macaques fed a moderately atherogenic diet and randomly assigned to three groups. The groups differed only in the source of dietary protein, which was either casein/lactalbumin (casein, n = 27), soy protein with the phytoestrogens intact (soy+, n = 27), or soy protein with the phytoestrogens mostly extracted (soy-, n = 28). The diets were fed for 14 months. Animals fed soy+ had significantly lower total and LDL plus VLDL cholesterol concentrations compared with the other two groups. They soy+ animals had the highest HDL cholesterol concentrations, the casein group had the lowest, and the soy- group was intermediate. A subset was necropsied for atherosclerosis evaluations (n = 11 per group). Morphometric and angiochemical measures were done to quantify atherosclerosis. Coronary artery atherosclerotic lesions were smallest in the soy+ group (90% less coronary atherosclerosis than the casein group and 50% less than the soy- group), largest in the casein group, and intermediate in the soy- group. The effects of the diets on lesion size and arterial lipid measures of the peripheral arteries were similar to those in the coronary arteries, with greatest prevention of atherogenesis with soy+ and intermediate benefit with soy- relative to casein. We could not determine whether the beneficial effects seen in the soy- group relate to the protein itself or to the remaining traces of phytoestrogens. The beneficial effects of soy protein on atherosclerosis appear to be mediated primarily by the phytoestrogen component. Testicular weights were unaffected by the phytoestrogens.

Arterioscler Thromb Vasc Biol 1997 Nov;17(11):2524-31

Phytoestrogens reduce bone loss and bone resorption in oophorectomized rats.

To examine a potential role for phytoestrogens in postmenopausal bone loss, the oophorectomized (OOX) rat model has been used in three studies to investigate the effects of the phytoestrogens coumestrol, zearalanol and a mixture of isoflavones on estrogen-dependent bone loss. In the studies of coumestrol and zearalanol, the rats were allocated to a control group, a phytoestrogen-treated group (1.5 micromol coumestrol or 3.1 mmol zearalanol twice per week, intramuscular) or, in the coumestrol study, an estrogen-treated group (28.1 nmol, intramuscular). In the isoflavone study, the rats were allocated to a control group, an estrogen treated group or a treatment group that received 131.25 mg of phytoestrogens per week incorporated into the nonpurified rat diet. Bone mineral density was measured globally and at the spine and femur at base line and six wk post-oophorectomy. In the coumestrol study, blood and urine samples were collected. Compared with the control group, rats receiving coumestrol and zearalanol had significantly reduced bone loss at all sites measured. The estrogen-treated group had significantly greater bone density than the control and the coumestrol-treated groups in the spine and global measurements. Coumestrol reduced urine calcium excretion and the bone resorption markers pyridinoline and deoxypyridinoline after one wk of treatment. Oral isoflavone phytoestrogens had no effect on oophorectomized rats including bone loss at the dose used. Thus, for the first time, the bioactivity of coumestrol and zearalanol in preventing bone loss has been demonstrated in a well-recognized model of postmenopausal bone loss.

J Nutr 1997 Sep;127(9):1795-9

Potassium iodide

Thyroid uptake and radiation dose after (131)I-lipiodol treatment: is thyroid blocking by potassium iodide necessary?

In radionuclide therapy with iodine-131 labelled pharmaceuticals, free (131)I may be released and trapped by the thyroid, causing an undesirable radiation burden. To prevent this, stable iodide such as potassium iodide (KI) can be given to saturate the thyroid before (131)I is administered. The guidelines of the European Association of Nuclear Medicine do not, however, recommend special precautions when administering (131)I-lipiodol therapy for hepatocellular carcinoma. Nevertheless, some authors have reported (131)I uptake in the thyroid as a consequence of such therapy. In this study, the influence of prophylactic KI on the thyroid uptake and dose (MIRD dosimetry) was prospectively investigated. (131)I-lipiodol was given as a slow bolus selectively in the proper hepatic artery or hyperselectively in the right and/or left hepatic artery. Patients were prospectively randomised into two groups. One group received KI in a dose of 100 mg per day starting two days before (131)I-lipiodol administration and continuing until two weeks after therapy (KI group; n=31), while the other group received no KI (non-KI group; n=37). Thyroid uptake was measured scintigraphically as a percentage of administered activity seven days after (131)I-lipiodol (n=68 treatments). The absorbed radiation dose to the thyroid was assessed by scintigraphy after seven and 14 days using a mono-exponential fitting model and MIRD dosimetry (n=40 treatments). The mean activity of (131)I-lipiodol administered was 1,835 MBq in a volume of 2 (n=17) or 4 (n=51) ml. Thyroid uptake was lower in the KI group, being 0.23%+/-0.06% of injected activity (n=31) compared with 0.42%+/-0.20% in the non-KI group (n=37); the mean thyroid dose was 5.5+/-1.6 Gy in the KI group (n=19) versus 11.9+/-5.9 Gy in the non-KI group (n=21). These differences were statistically significant (P<0.001). No effect of the amount of added cold lipiodol (4 vs 2 ml total volume) or selectivity of (131)I-lipiodol administration was evident (P>0.1). (131)I-lipiodol is associated with a generally low thyroid uptake and dose that may be significantly decreased by KI premedication. Given the low cost and the very good tolerance of the KI treatment, we believe the use of KI should be recommended in the majority of the patients.

Eur J Nucl Med Mol Imaging 2002 Oct;29(10):1311-6

Inactivation of the antibacterial activity of iodine potassium iodide and chlorhexidine digluconate against Enterococcus faecalis by dentin, dentin matrix, type-I collagen, and heat-killed microbial whole cells.

The antibacterial activity of chlorhexidine digluconate and potassium iodide on Enterococcus faecalis A197A was tested in the presence of dentin, dentin matrix, dentin pretreated by EDTA and citric acid, collagen, and heat-killed cells of Enterococcus faecalis and Candida albicans. Medications were preincubated for 1 h with each of the potential inhibitors and tested for their antibacterial activity against E. faecalis, strain A197A. Surviving bacteria were sampled after one and 24 h of incubation. Dentin matrix and heat-killed microbial cells were the most effective inhibitors of chlorhexidine, whereas dentin pretreated by citric acid or EDTA showed only slight inhibition. Dentin and skin collagen showed some inhibition at one h but not after 24 h. Iodine potassium iodide was effectively inhibited by dentin, dentin matrix, and heat-killed microbial cells. Skin collagen and dentin pretreated by EDTA or by citric acid showed little or no inhibitory effect on iodine potassium iodide. Different components of dentin are responsible for the divergent patterns of inhibition of the antibacterial activity of chlorhexidine digluconate and iodine potassium iodide. Chemical treatment of dentin before applying the medication into the root canal may alter the antibacterial effect of the medication.

J Endod 2002 Sep;28(9):634-7

Effect of iodine or iopanoic acid on thyroid Ca2+/NADPH-dependent H2O2-generating activity and thyroperoxidase in toxic diffuse goiters.

OBJECTIVE: The aim of the present study was to compare the effects of iopanoic acid (IOP) or a saturated solution of potassium iodide (SSKI) administration to patients with toxic diffuse goiters (TDG). DESIGN: Patients with TDG are treated with thionamides and high doses of iodine preoperatively. In this study, two types of preoperative drug regimens were used: propylthiouracil or methimazole plus SSKI for 10-15 days (n=8) or IOP for seven days (n=6). METHODS: Serum thyroid hormones (total and free thyroxine (T(4)), total tri-iodothyronine (T(3)) and reverse T(3) (rT(3)), were evaluated after seven days of either SSKI or IOP treatment, and after 10-15 days of SSKI administration. During thyroidectomy, samples of thyroid gland were obtained to evaluate thyroperoxidase and thyroid H(2)O(2)-generating activities. RESULTS: Serum total T(3) was significantly decreased after seven days of either treatment, and serum rT(3) was significantly increased in IOP-treated patients. Serum total and free T(4) were unaffected by seven days of IOP treatment, but decreased after seven days of SSKI treatment, although significantly diminished levels were only reached after a further three to eight days of SSKI administration. During both drug regimens, serum TSH remained low (SSKI: 0.159+/-0.122; IOP: 0.400+/-0.109 microU/ml). Thyroperoxidase activity was significantly lower in thyroid samples from patients treated with SSKI for 10 to 15 days than in the thyroid glands from IOP-treated patients. However, thyroid H(2)O(2) generation was inhibited in samples from patients treated with either IOP or SSKI. CONCLUSIONS: We show herein that IOP treatment can be effective in the management of hyperthyroidism and that this drug inhibits thyroid NADPH oxidase activity, just as previously described for SSKI, probably due to its iodine content.

Eur J Endocrinol 2002 Sep;147(3):293-8

High incidence of thyroid dysfunction despite prophylaxis with potassium iodide during (131)I-meta-iodobenzylguanidine treatment in children with neuroblastoma.

BACKGROUND: Treatment modalities like targeted radiotherapy with (131)I-meta-iodobenzylguanidine ((131)I-MIBG) improve survival rates after neuroblastoma (NB). Radiation to the thyroid gland can lead to hypothyroidism and even malignancy. Because hypothyroidism after (131)I-MIBG treatment was reported, the current KI prophylaxis against thyroidal radiation damage was evaluated. METHODS: The incidence, pathogenesis and consequences of thyroid dysfunction among 42 NB patients treated with (131)I-MIBG were evaluated retrospectively. Efficacy of KI prophylaxis was established by measuring thyroidal radioiodide uptake. Thyroid damage was expressed as thyrotropin elevation (TE, plasma concentration of thyroid stimulating hormone > or = 4.5 mU/L). RESULTS: The mean followup was 2.3 years (range, 0.1-8.5). The mean number of treatments with (131)I-MIBG was 3.3. Of 428 scintigrams, uptake of (131)I in the thyroid was visible in 92 (21.0%). Twenty two patients (52.4 %) presented TE after a mean period of 1.4 years (range, 0.1-5.8). Clinical signs of hypothyroidism were not observed. Eight patients received suppletion therapy with thyroxine. Thyrotropin elevation was transient in four patients. Of 25 survivors, with a mean followup of 3.5 years, 16 (64%) developed TE. No correlation was found between TE and thyroid visualization after (131)I-MIBG administration or the number of treatments. No abnormalities were seen by ultrasound imaging of the thyroid. CONCLUSIONS: Occurrence of thyroid dysfunction after treatment with (131)I-MIBG for NB is high, in spite of KI prophylaxis. Close followup of thyroid function and structure is required in patients treated with (131)I-MIBG. New ways of protecting the thyroid during exposure to radioiodine should be developed.

Cancer 2002 Apr 1;94(7):2081-9

Thyroidal uptake and radiation dose after repetitive I-131-MIBG treatments: influence of potassium iodide for thyroid blocking.

BACKGROUND: In I-131-MIBG therapy, I-131-iodide can be released from the I-131-MIBG molecule. Hypothyroidism might result from the undesirable irradiation of the thyroid gland. To prevent this, stable iodide such as potassium iodide (KI) is given to oversaturate the thyroid before I-131-MIBG is administered. PROCEDURE: In the present study, the incidence of hypothyroidism (elevated TSH) was correlated with the thyroidal uptake of I-131 and dose (MIRD dosimetry) after 35 individual treatments in ten patients. Iodine-131-MIBG therapy was performed using a modified dosage of 1.9-11.1 GBq (50-300 mCi) IV. Premedication with KI was done as recommended with a dose of 100 mg KI orally from two days before until four weeks after I-131-MIBG. RESULTS: The absorbed thyroidal dose amounted to a very variable range of 0.2 (patient # 1) up to 30.0 (patient 3) Gy with 7.1 +/- 7.9 Gy per treatment and 24.1+/- 19.2 Gy per patient (mean+/- SD), despite the same and compliantly taken KI premedication protocol. Up to now, 4/10 or 40% of patients have developed hypothyroidism after a mean follow-up period of 11 months and a mean total administered dose of 18.7 GBq (505 mCi). A trend towards higher thyroidal doses was seen in the hypothyroid patients. CONCLUSIONS: This study observes a general high inter- and intra-individual variability in radio-iodide uptake in the thyroid after I-131-MIBG therapy despite KI premedication, as well as possible occurrence of hypothyroidism. A dose-response relationship needs confirmation on a larger cohort of patients to reach statistical value. An alternative thyroid cytoprotection strategy for possible long-term survivors may be considered.

Med Pediatr Oncol 2002 Jan;38(1):41-6

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