LE Magazine 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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