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Effect of diet on
excretion of estrogens in pre- and postmenopausal
women.
Goldin BR, Adlercreutz H, Dwyer JT, Swenson L, Warram
JH, Gorbach SL.
Cancer Res 1981 Sep;41(9 Pt 2):3771-3
Fecal, urinary, and plasma estrogens and plasma
androgens were studied in healthy pre- and postmenopausal
vegetarian and omnivorous women. Dietary histories of the
subjects revealed that omnivores consumed a higher
percentage of total protein and fat from animal sources.
The total 72-hr fecal excretion as measured by dry weight
was higher for vegetarians. Preliminary results indicate
that vegetarian women excrete 2 to 3 times more estrogens
in feces than do omnivores and that omnivores have about
50% higher mean plasma level of unconjugated estrone and
estradiol than vegetarians. Estriol-3-glucuronide, a
compound that is formed upon reabsorption of free estriol
from the intestine, is found in lower concentrations in the
urine of vegetarians. These data suggest that in
vegetarians a greater amount of the biliary estrogens
escape reabsorption and are excreted with the feces. The
differences in estrogen metabolism may explain the lower
incidence of breast cancer in vegetarian women.
Estrogen excretion
patterns and plasma levels in vegetarian and omnivorous
women.
Goldin BR, Adlercreutz H, Gorbach SL, Warram JH, Dwyer
JT, Swenson L, Woods MN.
N Engl J Med 1982 Dec 16;307(25):1542-7
We studied 10 vegetarian and 10 nonvegetarian
premenopausal women on four occasions approximately four
months apart. During each study period, the participants
kept three-day dietary records, and estrogens were measured
in plasma, urinary, and fecal samples. Vegetarians consumed
less total fat than omnivores did (30 per cent of total
calories, as compared with 40 per cent) and more dietary
fiber (28 g per day, as compared with 12 g). There was a
positive correlation between fecal weight and fecal
excretion of estrogens in both groups (P less than 0.001),
with vegetarians having higher fecal weight and increased
fecal excretion of estrogens. Urinary excretion of estriol
was lower in vegetarians (P less than 0.05), and their
plasma levels of estrone and estradiol were negatively
correlated with fecal excretion of estrogen (P = 0.005).
Among the vegetarians the beta-glucuronidase activity of
fecal bacteria was significantly reduced (P = 0.05). We
conclude that vegetarian women have an increased fecal
output, which leads to increased fecal excretion of
estrogen and a decreased plasma concentration of
estrogen.
Fibrocytic breast
disease: current status of diagnosis and
treatment.
Greenblatt RB; Vasquez J; Samaras C
Postgrad Med (UNITED STATES) Mar 1982, 71 (3) p159-63,
166-8
Improved diagnostic procedures and use of a new
steroidal agent, danazol (Danocrine), should reduce the
need for surgical intervention in fibrocystic breast
disease. Thermography, a non-invasive procedure that may be
used with impunity, may help identify women at high risk.
Mammography, which is useful in revealing malignancy in an
early stage, should be done in women with tow consecutive
abnormal thermograms. Biopsies should be performed,
however, on suspicious, firm, irregular masses, regardless
of results on thermography or mammography. Use of danazol
may be advantageous not only in ameliorating pain and
eliminating nodosities, but also in guiding the surgeon to
the nodule that is unresponsive to treatment and therefore
should be evaluated by biopsy.
Extrahepatic biliary
obstruction: can silymarin protect liver
function?
Hagymasi K, Kocsis I, Lugasi A, Feher J, Blazovics A.
2nd Department of Internal Medicine, Semmelweiss
University, Szentkiralyi u 26, H-1088 Budapest, Hungary.
hkriszti@bel2.sote.hu
Phytother Res 2002 Mar;16 Suppl 1:S78-80
The hepatoprotective property of silymarin is well
known. However, it is not known whether the antioxidant
silymarin might have a beneficial effect in extrahepatic
cholestasis in common bile duct ligated rats. Malonaldehyde
property concentrations, the hydrogen-donating ability and
reducing power were measured in liver homogenates by
spectrophotometry, as well as free SH-group levels and
glutathione-reductase activities in sera. The total
scavenger capacity of the livers was quantified by a
chemiluminometric method. The elevated lipid peroxidation
and decreased antioxidant capacity of liver homogenates and
sera could be observed in ligated rats. Silymarin
pretreatment improved the antioxidant capacity of the
liver, diminished the direct bilirubin concentration and
caused an increase of liver enzyme activities compared with
the groups without treatment. These effects of silymarin
suggest that it may be a useful agent for improving the
antioxidant defensive system in extrahepatic
Breast
cancer.
Henderson, M., Pike, M.C., Bernstein, L., Ross, R.K.
In Cancer Epidemiology and Prevention, Second Edition
1996. Schottenfeld, D., Fraumeni, J.F., Eds. New York:
Oxford University Press.
Potential mechanisms of
diet therapy for fibrocystic breast conditions show
inadequate evidence of effectiveness.
Horner NK, Lampe JW. Division of Public Health Sciences,
Fred Hutchinson Cancer Research Center, Seattle, WA
98109-1024, USA.
J Am Diet Assoc 2000 Nov;100(11):1368-80
Fibrocystic breast conditions, formerly referred to as
fibrocystic breast disease, affect about half of all women
and typically present as any combination of breast
nodularity, swelling, and pain. We reviewed the literature
to evaluate evidence supporting nutrition interventions
commonly recommended for fibrocystic breast conditions by
health care providers. Randomized, controlled studies of
the effectiveness of caffeine restriction fail to support
any benefit in fibrocystic breast conditions. Similarly,
evidence supporting evening primrose oil, vitamin E, or
pyridoxine as treatments for the discomforts of fibrocystic
breast conditions is insufficient to draw conclusions about
effectiveness. Dietary alterations that influence the
intermediate markers for fibrocystic breast conditions
include low-fat (15% to 20% energy), high-fiber (30 g/day),
and soy isoflavone regimens. However, our findings provide
no solid evidence for secondary prevention or treatment of
fibrocystic breast conditions through a dietary approach.
Health care providers should limit recommendations to
proven diet therapies supported by randomized,
placebo-controlled trials, given the instability inherent
in fibrocystic breast conditions and the near 20% placebo
effect associated with intervention. Because excessive
estrogen or altered sensitivity to estrogen is the dominant
theory of etiology, interventions that may modulate
endogenous steroid hormones warrant further investigation
as potential treatments for symptomatic fibrocystic breast
conditions.
Waist circumference,
waist:hip ratio, and risk of breast cancer in the Nurses'
Health Study.
Huang Z, Willett WC, Colditz GA, Hunter DJ, Manson JE,
Rosner B, Speizer FE, Hankinson SE. Department of
Nutrition, Harvard School of Public Health, Boston, MA
02115, USA.
Am J Epidemiol 1999 Dec 15;150(12):1316-24
This study examined prospectively the associations of
waist circumference and waist:hip circumference ratio with
risk of breast cancer. A total of 47,382 US registered
nurses who reported their waist and hip circumferences in
1986 were followed up through May 1994 for identification
of incident cases of breast cancer. During 333,097
person-years of follow-up, 1,037 invasive breast cancers
were diagnosed. In proportional hazards analyses, waist
circumference was nonsignificantly related to risk of
premenopausal breast cancer but was significantly
associated with postmenopausal breast cancer after
adjustment for established breast cancer risk factors (for
the highest quintile of waist circumference vs. the lowest,
relative risk (RR) = 1.34; 95% confidence interval (CI):
1.05, 1.72). When the analysis was limited to
postmenopausal women who had never received hormone
replacement therapy, a stronger positive association was
found (RR = 1.88; 95% CI: 1.25, 2.85). After the data were
further controlled for body mass index, the positive
association was only slightly attenuated (RR = 1.83; 95%
CI: 1.12, 2.99). Among past and current postmenopausal
hormone users, no significant associations were found.
Similar but slightly weaker associations were observed
between waist:hip ratio and breast cancer risk. These data
suggest that greater waist circumference increases risk of
breast cancer, especially among postmenopausal women who
are otherwise at lower risk because of never having used
estrogen replacement hormones.
Relationship between
carbohydrate-induced hypertriglyceridemia and fatty acid
synthesis in lean and obese subjects.
Hudgins LC, Hellerstein MK, Seidman CE, Neese RA,
Tremaroli JD, Hirsch J. Rockefeller University, 1230 York
Avenue, New York, NY 10021-6399, USA.
J Lipid Res 2000 Apr;41(4):595-604
We previously reported that a eucaloric, low fat, liquid
formula diet enriched in simple carbohydrate markedly
increased the synthesis of fatty acids in lean volunteers.
To examine the diet sensitivity of obese subjects, 7 obese
and 12 lean volunteers were given two eucaloric low fat
solid food diets enriched in simple sugars for 2 weeks each
in a random-order, cross-over design (10% fat, 75%
carbohydrate vs. 30% fat, 55% carbohydrate, ratio of sugar
to starch 60:40). The fatty acid compositions of both diets
were matched to the composition of each subject's adipose
tissue and fatty acid synthesis measured by the method of
linoleate dilution in plasma VLDL triglyceride. In all
subjects, the maximum % de novo synthesized fatty acids in
VLDL triglyceride 3;-9 h after the last meal was higher on
the 10% versus the 30% fat diet. There was no significant
difference between the dietary effects on lean (4313 vs.
1213%) and obese (3715 vs. 66%) subjects, despite 2-fold
elevated levels of insulin and reduced glucagon levels in
the obese. Similar results were obtained for de novo
palmitate synthesis in VLDL triglyceride measured by mass
isotopomer distribution analysis after infusion of
[(13)C]acetate. On the 10% fat diet, plasma triglycerides
(fasting and 24 h) were increased and correlated with fatty
acid synthesis. Triglycerides were higher when fatty acid
synthesis was constantly elevated rather than having
diurnal variation.Thus, eucaloric, solid food diets which
are very low in fat and high in simple sugars markedly
stimulate fatty acid synthesis from carbohydrate, and
plasma triglycerides increase in proportion to the amount
of fatty acid synthesis. However, this dietary effect is
not related to body mass index, insulin, or glucagon
levels.
Biochemical and
anthropometric characterization of morbid obesity in a
large Utah pedigree.
Hunt SC, Williams RR, Adams TD. Department of Internal
Medicine, University of Utah School of Medicine, Salt Lake
City, USA.
Obes Res 1995 Sep;3 Suppl 2:165S-172S
A Utah family with morbid obesity was extended to
include 122 persons in four generations for the purpose of
characterizing anthropometric and biochemical variables in
family members with and without morbid obesity.
Seventy-seven subjects had blood drawn for biochemical
analyses. Of the 77 subjects, 12 were morbidly obese (>
or = 44.5 kg or 100 pounds overweight), 20 were between
22.5-45.4 kg (50 and 99 pounds) overweight and 45 were less
than 22.5 kg (50 pounds) overweight. Sixty-two
randomly-ascertained controls were used for comparisons of
age- and gender-adjusted study variables. Morbidly obese
subjects had mean body mass indices (BMI) of 41.0 kg/m2 (62
kg over ideal weight) compared to 25.3 kg/m2 (10 kg
overweight) in the < 22.5 kg family members (p <
0.001). The < 22.5 kg family members had lower BMI than
the random controls (27.6 kg/m2, p < 0.05), indicating
clear bimodality of obesity within the pedigree. Percent
body fat from bioelectrical impedance was 35% versus 24% in
the morbidly obese and the < 22.5 kg subjects,
respectively. Idealbody weight was similar among the three
pedigree weight groups. Hip and waist circumferences were
much larger in the morbidly obese and the waist-to-hip
ratio remained significantly greater in the morbidly obese
subjects compared to the < 22.5 kg group. Morbidly obese
subjects had elevated triglycerides and VLDL-C levels, low
HDL-levels, and normal LDL-C levels. Fasting insulin was
the best predictor of morbid obesity of all biochemical and
lipid measurements (odds ratio of 4.5). Fasting insulin
levels and the insulin-to-glucose ratio were more than
twice as high as control levels.(ABSTRACT TRUNCATED AT 250
WORDS)
Prevalence, Screening
and Management of Atypical Hyperplasia and Lobular
Carcinoma In Situ 1997.
Hurley, S.F., Hart, S., Susil, B.
Canberra: National Health and Medical Research
Council/National Breast Cancer Centre.
Breast health
(non-cancerous breast issues).
Imaginis.
Imaginis Newsletter 2000 Nov 13.
Durham, NC: Imaginis Corporation.
Soy and breast
cancer.
Imaginis.
Imaginis Newsletter 2001 Jan 20.
Durham, NC: Imaginis Corporation.
Relation between the
serum level of C-peptide and risk factors for coronary
heart disease and diabetic microangiopathy in patients with
type-2 diabetes mellitus.
Inukai T, Matsutomo R, Tayama K, Aso Y, Takemura Y.
Department of Medicine, Koshigaya Hospital, Dokkyo
University School of Medicine, Japan.
Exp Clin Endocrinol Diabetes 1999;107(1):40-5
Syndrome X is used to describe a constellation of
factors that lead to coronary heart disease (CHD):
hypertension, hyperinsulinemia, impaired glucose tolerance,
and an abnormality in lipid metabolism. We investigated the
relationship between serum levels of C-peptide
immunoreactivity (CPR) and diabetic complications in 256
patients with type-2 diabetes mellitus. The serum level of
CPR was measured by radioimmunoassay (RIA). Diabetic
patients were divided into 3 groups according to the serum
level of CPR as follows: low CPR (n = 19, <0.7 ng/ml),
normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n =
63, >2.2 ng/ml). The body mass index (BMI) and the serum
level of triglycerides were significantly higher in the
high CPR group (P < 0.05, respectively) compared with
normal CPR group. The prevalence of hypertension was
significantly higher in the high CPR group than in the
other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR:
38%). The frequency of the number of patients receiving
insulin therapy was greater in the low CPR group than in
the other 2 groups, (low CPR: 58%, normal CPR: 15%, high
CPR: 11%). The serum CPR level was significantly lower in
patients with than without proliferative retinopathy or
macroalbuminuria. Our conclusion is that the present data
suggest that an increased serum level of CPR is associated
with obesity, elevated serum triglycerides, and
hypertension in patients with type-2 diabetes mellitus. A
low CPR level leading to hyperglycemia is associated with
the progression of diabetic microangiopathies, such as
retinopathy and nephropathy.
Conjugated linoleic
acid inhibits proliferation and induces apoptosis of normal
rat mammary epithelial cells in primary
culture.
Ip MM, Masso-Welch PA, Shoemaker SF, Shea-Eaton WK, Ip
C. Department of Pharmacology and Therapeutics, Roswell
Park Cancer Institute, Buffalo, New York, 14263, USA.
mip@sc3101.med.buffalo.edu
Exp Cell Res 1999 Jul 10;250(1):22-34
The trace fatty acid conjugated linoleic acid (CLA)
inhibits rat mammary carcinogenesis when fed prior to
carcinogen during pubertal mammary gland development or
during the promotion phase of carcinogenesis. The following
studies were done to investigate possible mechanisms of
these effects. Using a physiological model for growth and
differentiation of normal rat mammary epithelial cell
organoids (MEO) in primary culture, we found that CLA, but
not linoleic acid (LA), inhibited growth of MEO and that
this growth inhibition was mediated both by a reduction in
DNA synthesis and a stimulation of apoptosis. The effects
of CLA did not appear to be mediated by changes in
epithelial protein kinase C (PKC) since neither total
activity nor expression nor localization of PKC isoenzymes
alpha, betaII, delta, varepsilon, eta, or zeta were altered
in the epithelium of CLA-fed rats. In contrast, PKCs delta,
varepsilon, and eta were specifically upregulated and
associated with a lipid-like, but acetone-insoluble,
fibrillar material found exclusively in adipocytes from
CLA-fed rats. Taken together, these observations
demonstrate that CLA can act directly to inhibit growth and
induce apoptosis of normal MEO and may thus prevent breast
cancer by its ability to reduce mammary epithelial density
and to inhibit the outgrowth of initiated MEO. Moreover,
the changes in mammary adipocyte PKC expression and lipid
composition suggest that the adipose stroma may play an
important in vivo role in mediating the ability of CLA to
inhibit mammary carcinogenesis. Copyright 1999 Academic
Press.
Conjugated linoleic
acid-enriched butter fat alters mammary gland morphogenesis
and reduces cancer risk in rats.
Ip C, Banni S, Angioni E, Carta G, McGinley J, Thompson
HJ, Barbano D, Bauman D. Department of Experimental
Pathology, Roswell Park Cancer Institute, Buffalo, NY
14263, USA.
J Nutr 1999 Dec;129(12):2135-42
Conjugated linoleic acid (CLA) is a potent cancer
preventive agent in animal models. To date, all of the in
vivo work with CLA has been done with a commercial free
fatty acid preparation containing a mixture of c9,t11-,
t10,c12- and c11,t13-isomers, although CLA in food is
predominantly (80-90%) the c9,t11-isomer present in
triacylglycerols. The objective of this study was to
determine whether a high CLA butter fat has biological
activities similar to those of the mixture of free fatty
acid CLA isomers. The following four different endpoints
were evaluated in rat mammary gland: 1) digitized image
analysis of epithelial mass in mammary whole mount; 2)
terminal end bud (TEB) density; 3) proliferative activity
of TEB cells as determined by proliferating cell nuclear
antigen immunohistochemistry; and 4) mammary cancer
prevention bioassay in the methylnitrosourea model. It
should be noted that TEB cells are the target cells for
mammary chemical carcinogenesis. Feeding butter fat CLA to
rats during the time of pubescent mammary gland development
reduced mammary epithelial mass by 22%, decreased the size
of the TEB population by 30%, suppressed the proliferation
of TEB cells by 30% and inhibited mammary tumor yield by
53% (P < 0.05). Furthermore, all of the above variables
responded with the same magnitude of change to both butter
fat CLA and the mixture of CLA isomers at the level of CLA
(0.8%) present in the diet. Interestingly, there appeared
to be some selectivity in the uptake or incorporation of
c9,t11-CLA over t10,c12-CLA in the tissues of rats given
the mixture of CLA isomers. Rats consuming the CLA-enriched
butter fat also consistently accumulated more total CLA in
the mammary gland and other tissues (four- to sixfold
increases) compared with those consuming free fatty acid
CLA (threefold increases) at the same dietary level of
intake. We hypothesize that the availability of vaccenic
acid (t11-18:1) in butter fat may serve as the precursor
for the endogenous synthesis of CLA via the
Delta9-desaturase reaction. Further studies will be
conducted to investigate other attributes of this novel
dairy product.
Stereotactic histologic
biopsy in breasts with implants.
Jackman RJ, Lamm RL. Department of Radiology, Palo Alto
Medical Clinic, 795 El Camino Real, Palo Alto, CA 94301.
From the 1999 RSNA scientific assembly. Received January 4,
2001.
Radiology 2002 Jan;222(1):157-64
PURPOSE: To describe our experience with stereotactic
histologic biopsy in patients with breast implants.
MATERIALS AND METHODS: Thirty-one (1.3%) of 2,399
consecutive lesions on which stereotactic histologic biopsy
was performed were in breasts containing implants. Biopsy
difficulties were evaluated for lesions in breasts with and
breasts without implants. Biopsy was performed on lesions
in patients with implants prone on a dedicated table, with
automated large-core (n = 13) or directional
vacuum-assisted (n = 18) devices. Follow-up was surgical
(11 of 11 malignancies and two of three high-risk lesions)
and mammographic (one of three high-risk lesions and 17 of
17 benign lesions). RESULTS: There were no implant
ruptures, hematomas requiring drainage, infections
requiring treatment, false-negative findings, or histologic
underestimations. Difficulties with stereotactic histologic
biopsy were more prevalent in breasts with implants and
included positioning problems in 10 (50%) of 20 lesions in
breasts with subglandular implants and zero (0%) of 10 with
subpectoral implants, lesions seen on only one view in four
(13%) of 31 lesions, specimen radiographs negative for
calcifications in two (10%) of 20 lesions, prominent
bleeding in two (6%) of 31 lesions, and suboptimally small
tissue samples in three (10%) of 31 lesions. CONCLUSION:
Stereotactic histologic biopsy is safe in breasts with
implants. Compared with that in breasts without implants,
biopsy is often technically more difficult and may
eventually prove less accurate.
Fish consumption and
breast cancer risk: an ecological study.
Kaizer L, Boyd NF, Kriukov V, Tritchler D. Ludwig
Institute for Cancer Research (Toronto Branch), Ontario,
Canada.
Nutr Cancer 1989;12(1):61-8
There is experimental evidence that fish oils protect
against mammary carcinogens in animals. However, there has
been little investigation of the possible relevance of this
finding to breast cancer in humans. We compared breast
cancer incidence and mortality rates with estimates of the
consumption of fish and other foods and nutrients in the
countries for which reliable data are available. The
results showed an inverse association between percent
calories from fish and breast cancer rates that was
consistent with a protective effect. This analysis
confirmed the finding of others that dietary fat is
strongly associated with international variation in breast
cancer rates. It also showed that of the dietary components
considered, percent calories from fish was the factor most
strongly correlated with breast cancer rates after
statistical adjustment for dietary fat intake. This result
is therefore in accord with animal experimental data and
suggests that the omega-3 fatty acids contained in certain
fish may protect against breast cancer.
The deadly quartet.
Upper-body obesity, glucose intolerance,
hpertriglyceridemia, and hypertension.
Kaplan NM. Department of Internal Medicine, University
of Texas Southwestern Medical Center, Dallas
75235-9030.
Arch Intern Med 1989 Jul;149(7):1514-20
The contribution of obesity to cardiovascular risk has
not been adequately appreciated because of a failure to
recognize the involvement of upper-body predominance of
body weight with hypertension, diabetes, and
hypertriglyceridemia even in the absence of significant
overall obesity. This article examines the evidence that
upper-body obesity, as usually induced by caloric excess in
the presence of androgens, mediates these problems by way
of hyperinsulinemia. Because of these interrelationships,
there is a need to identify and prevent upper-body obesity
or, failing that, to provide therapies that will control
the associated problems without aggravating
hyperinsulinemia.
Dehydroepiandrosterone
decreases serum tumor necrosis factor-alpha and restores
insulin sensitivity: independent effect from secondary
weight reduction in genetically obese Zucker fatty
rats.
Kimura M, Tanaka S, Yamada Y, Kiuchi Y, Yamakawa T,
Sekihara H. The Third Department of Internal Medicine,
Yokohama City University School of Medicine, Yokohama,
Japan.
Endocrinology 1998 Jul;139(7):3249-53
Dehydroepiandrosterone (DHEA) and its sulfate ester are
the most abundant circulating adrenal steroids in humans.
Administration of DHEA has been reported to have beneficial
effects on obesity, hyperlipidemia, diabetes, and
atherosclerosis in obese rodents, although its effects on
insulin resistance have not been fully elucidated. In this
study, the effects of DHEA treatment on insulin sensitivity
were investigated in genetically obese Zucker rats, an
animal model of insulin resistance, using the euglycemic
clamp technique. After 0.4% DHEA was administered for 10
days to female obese Zucker rats aged 16 weeks, body weight
and plasma insulin decreased and glucose disposal rate
(GDR), which was normally reduced in obese rats, rose
significantly compared with age-and sex-matched control
obese rats. On the other hand, although the pair-fed obese
rats also showed levels of weight reduction similar to
those of DHEA-treated rats, the increase in GDR of
DHEA-treated rats was significantly greater than in
pair-fed rats, suggesting a direct ameliorating effect of
DHEA on insulin sensitivity of obese rats. Serum
concentration of tumor necrosis factor (TNF)-alpha, one of
cytokines causing insulin resistance, was also reduced
significantly in DHEA-treated, but not in pair-fed obese
rats. In conclusion, our results suggest that DHEA
treatment reduces body weight and serum TNF-alpha
independently, and that both may ameliorate insulin
resistance in obese Zucker fatty rats.
Antioxidant properties
of silybin glycosides.
Kosina P, Kren V, Gebhardt R, Grambal F, Ulrichova J,
Walterova D. Centre for Bioanalytical Research, Palacky
University, Hnevotinska 3, 775 15 Olomouc, Czech
Republic.
Phytother Res 2002 Mar;16 Suppl 1:S33-9
New soluble derivatives of the hepatoprotective
flavonolignan silybin (1), namely silybin galactoside (2),
glucoside (3), lactoside (4) and maltoside (5) were
investigated for their radical scavenging and
antilipoperoxidation properties. According to cyclic
voltammetry the results show that glycosides are weaker
electron donors than silybin, although it was of interest
that they were found to be more potent scavengers of the
1,1-diphenyl-2-picrylhydrazyl and the
2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic
acid)-derived radicals. The glycosides (2)-(5) were more
efficient than silybin in preventing
tert-butylhydroperoxide-induced lipoperoxidation of rat
liver mitochondrial membranes. Furthermore, glycosides
(2)-(5) were significantly more cytoprotective than silybin
in tert-butylhydroperoxide-damaged rat erythrocytes and
primary hepatocyte cultures. Glycosylation of silybin
substantially reduced its toxic effects in primary cultured
hepatocytes observed during prolonged incubation. These
results suggest that silybin glycosides are suitable
soluble derivatives of silybin for experimental studies and
may have therapeutic potential. Copyright 2002 John Wiley
&amp; Sons, Ltd.
Prolactin response to
thyrotropin-releasing hormone stimulation and dopaminergic
inhibition in benign breast disease.
Kumar S, Mansel RE, Hughes LE, Woodhead JS, Edwards CA,
Scanlon MF, Newcombe RG.
Cancer 1984 Mar 15;53(6):1311-5
Pituitary function was tested in predefined clinical
groups of benign breast disease under strictly controlled
clinical and laboratory conditions. Two different tests of
prolactin storage and control mechanisms, direct
stimulation by thyrotropin-releasing hormone (TRH) and
inhibition of dopaminergic control by domperidone, indicate
a significant abnormality in patients with severe cyclical
mastalgia and nodular breast disease (P less than 0.05 and
P less than 0.002), but not in those with noncyclical
mastalgia. No abnormalities of thyroid function were
found.
Prediction of response
to endocrine therapy in pronounced cyclical mastalgia using
dynamic tests of prolactin release.
Kumar S, Mansel RE, Hughes LE, Edwards CA, Scanlon
MF.
Clin Endocrinol (Oxf) 1985 Dec;23(6):699-704
Many of the endocrine agents currently used to treat
symptomatic benign breast disease modify the action or
secretion of prolactin. We have compared the responses to
hormonal therapy with dynamic assessment of prolactin
control in 29 patients with cyclical mastalgia and in 7
patients with non-cyclical mastalgia. The tests of
prolactin release used were direct stimulation by TRH or
dopaminergic blockade by domperidone. These were carried
out before treatment in the mastalgic patients and also in
22 age-matched asymptomatic controls. The response to
treatment was assessed using a special pain chart and
visual linear analogue scale. Patients with cyclical
mastalgia could be divided into two groups: those in whom
the peak prolactin release was exaggerated (greater than
4000 mU/l) and those in whom the prolactin release was less
marked and similar to control subjects and patients with
non-cyclical mastalgia. Patients in the cyclical mastalgia
group with a high peak prolactin release responded to
hormonal treatment significantly more frequently (90%) than
those with a normal prolactin release (50%). Basal
prolactin levels did not correlate with the response to
treatment. In the non-cyclical mastalgia group, no patient
had peak prolactin release greater than 4000 mU/l and none
responded to therapy. This study indicates that dynamic
tests of prolactin release in cyclical mastalgia may be
useful in predicting the subsequent satisfactory response
to endocrine therapy if a high peak prolactin release is
induced.
The effect of
dehydroepiandrosterone combined with a low-fat diet in
spontaneously obese dogs: a clinical trial.
Kurzman ID, Panciera DL, Miller JB, MacEwen EG.
Department of Medical Sciences, University of Wisconsin,
School of Veterinary Medicine, Madison 53706, USA.
Obes Res 1998 Jan;6(1):20-8
Dehydroepiandrosterone (DHEA) has been shown to have
antiobesity activity in rodents and spontaneously obese
dogs. This study evaluated the effect of DHEA or placebo
combined with a low-fat/high-fiber diet in spontaneously
obese dogs in a clinical trial. Spontaneously obese,
euthyroid dogs, referred to the University of Wisconsin
School of Veterinary Medicine for treatment of their
obesity, were evaluated for percent overweight, rate of
weight loss, serum cholesterol, plasma lipoprotein and
serum biochemistry profiles, complete blood count, and
endocrine profiles (T4, T3, cortisol, insulin, and
DHEA-sulfate). DHEA-treated dogs had a significantly
increased rate of actual and percent excess weight loss
compared with placebo-treated dogs. Serum cholesterol
decreased in both treatment groups; however, DHEA-treated
dogs had a significantly greater reduction than
placebo-treated dogs. DHEA-treated dogs had a significant
32% reduction in total plasma cholesterol, which was due to
a 27% reduction in the lipoprotein fraction containing the
high-density lipoprotein (HDL) and a 50% reduction in the
lipoprotein fraction containing the low-density lipoprotein
(LDL). Placebo-treated dogs did not have a significant
reduction in total plasma cholesterol or in the fraction
containing LDL; however, they did have a significant 11%
reduction in the fraction containing HDL. Significant
decreases in serum T4 and T3 observed in dogs receiving
DHEA were not noted in dogs receiving placebo. DHEA in
combination with caloric restriction results in a faster
rate of weight loss than does caloric restriction alone. In
addition, DHEA has hypocholesterolemic activity,
particularly affecting the lipoprotein fraction containing
the LDL cholesterol.
The Woman's Health
Companion 1996.
Lark, S.M.
Berkeley, CA: Celestial Arts.
Benign breast disease
and consumption of beverages containing
methylxanthines.
La Vecchia C, Franceschi S, Parazzini F, Regallo M,
Decarli A, Gallus G, Di Pietro S, Tognoni G.
Natl Cancer Inst 1985 May;74(5):995-1000
The relationship between methylxanthine (Mx) consumption
and benign breast disease was evaluated in a case-control
study of 288 women with histologically confirmed benign
breast lumps (203 dysplastic lesions and 85 benign tumors)
and 2 groups of control women--285 patients in the hospital
for acute conditions apparently unrelated to the
consumption of Mx-containing beverages and 291 outpatients.
The relative risk estimates of dysplastic breast lesions
(fibrocystic disease), with allowance for all identified
potential distorting factors, for women who drank 1-2 or 3
or more cups of coffee per day were 4.1 and 6.4,
respectively, when the hospital controls were the
comparison group and 2.0 and 3.7, respectively, when the
outpatient controls were the comparison group. The
relationship was even stronger when the total consumption
of Mx-containing beverages (coffee plus tea) was considered
and increased with increasing duration of use. The
association was not explained by any of the major risk
factors for fibrocystic breast diseases or by differences
in general characteristics or other lifestyle habits
between cases and controls. Mx consumption was not related
to the risk of benign breast tumors (fibroadenomas). These
findings support the hypothesis that Mx consumption is
related to the risk of dysplastic lesions of the
breast.
Cholesterol and bile
acid metabolism in obesity.
Leijd B.
Clin Sci (Lond). 1980 Sep;59(3):203-6.
1. The present study was undertaken to determine the
influence of obesity on bile acid kinetics and cholesterol
balance in man. 2. Fourteen obese and normolipidaemic
patients (160 +/- 6% of ideal body weight, mean +/- SEM)
were studied under standardized dietary conditions. Bile
acid kinetics, were determined with the aid of 14C-labelled
cholic acid and chenodeoxycholic acid. Cholesterol balance
was calculated as the sum of bile acid synthesis plus daily
faecal excretion of neutral C27 steroids minus dietary
intake of cholesterol. The results obtained were compared
with previously published data on control subjects (n =
13). 3. The cholesterol balance was higher in the obese
patients (2.61 +/- 0.27 mmol/day) than in the control
subjects (1.78 +/- 0.22 mmol/day), owing to a higher
excretion of neutral steroids. When expressed per kg of
body weight the cholesterol balance was quite normal in the
obese patients.
[Hormonal contraception
and benign breast disease. Evaluation of a treatment
protocol for chronic mastopathy with mastalgia]
[Article in Italian]
Leonardi M. Divisione di Ginecologia e Ostetricia,
Azienda USSL Ambito Territoriale N. 14, Presidio
Ospedaliero di Iseo (Brescia).
Minerva Ginecol 1997 Jun;49(6):271-6
INTRODUCTION AND AIMS: The aim of this study was to
study patients suffering from mammary nodules, fibrocystic
disease and mastodynia. Having established the absence of
malignant disease, the effect of EP (oestroprogestin) was
evaluated in the treatment of fibrocystic disease with
mastalgia.
METHODS: From January 1990 to December 1995 a total of
1921 women underwent breast examination at the "Centro di
Fisiopatologia della Mammella" in the Division of
Gynecology and Obstetrics of Iseo Municipal Hospital.
Subjects were aged between 9 and 84 years old. The
experimental protocol included a retrospective study of a
group of 89 patients suffering from chronic fibrocystic
disease with mastalgia with a 3-month follow-up. The
clinical examination was commenced by recording the
patient's history and the measurement of the thickness of
the gland and the evaluation of mastalgia represented
important stages of the eco-clinical assessment. The
setting for the study was the breast pathology out-patient
clinic of the Division of Gynecology and Obstetrics. These
women regularly attended our outpatient clinics for the
following reasons: depistage, mastodynia, mammary
secretion, self-diagnosis of mammary nodules, checkups in
patients during follow-up after surgery for genital
neoplasia. All patients underwent clinical, echographic and
often mammography/X-ray. Patients were selected on the
basis of the following criteria: absence of malignant
pathology and presence of chronic fibrocystic disease with
mastalgia. Of those admitted to the study (no. = 89), only
59 completed the course. In addition to the absence of
malignant pathology and the presence of chronic fibrocystic
disease with mastalgia, the following parameters were
assessed: measurement of the thickness of the mammary gland
involving QSE before and after 3-month treatment with EP.
The EP used were: gestodene 0.075 mg and etynylestradiol
0.03 mg-Minulet, or etynylestradiol 0.02 mg and dexogestrel
0.150 mg-Securgin and Mercilon.
RESULTS: The response to treatment was classified
according to the 4 levels of the Cardiff Breast Score
(CBS). The results were relatively good: 35.59% of patients
showed a reduction in symptoms; 25.42% showed a marked
improvement, and 18.64% a remission of symptoms. No effect
was reported in 20.33% of patients.
CONCLUSIONS: In conclusion, it may be said that EP
treatment for 3 months can at least be proposed in patients
with chronic fibrocystic disease and mastalgia given that a
reduction and improvement in symptoms was seen in 60% of
patients.
DHEA(S): the fountain
of youth.
Leowattana W. Department of Clinical Pathology, Faculty
of Medicine Siriraj Hospital, Mahidol University, Bangkok,
Thailand.
J Med Assoc Thai 2001 Oct;84 Suppl 2:S605-12
Dehydroepiandrosterone (DHEA) and its sulfate ester
(DHEAS) are weak androgens produced primarily by the
adrenal gland. Although their plasma concentrations by far
exceed those of any other adrenal product, their
physiological roles have not yet been determined. In
plasma, where the major portion of these hormones is
present in the sulfate form, it is possible that DHEAS
serves as a reservoir for DHEA. Since various tissues have
been shown to contain steroid sulfatases. The peak plasma
levels of DHEA and DHEAS occur at approximately age 25
years, decrease progressively thereafter, and diminish by
95 per cent around the age of 85 years. The decline of
DHEAS concentrations with aging has led to the suggestion
that DHEAS could play a role in itself and be implicated in
longevity. Moreover, the epidemiological evidence has shown
that adult men with high plasma DHEAS levels are less
likely to die of cardiovascular disease. DHEA has also been
shown to increase the body's ability to transform food into
energy and burn off excess fat. Another recent finding
involves the anti-inflammatory properties of DHEA. It has
been known that DHEA can lower the levels of interleukin-6
(IL-6) and tumor necrosis factor alpha (TNF-alpha). It
should be pointed out that chronic inflammation is known to
play a critical role in the development of the killer
diseases of aging: heart disease, Alzheimer's disease and
certain types of cancer. In conclusion, DHEA or DHEAS
administration combined with conventional treatment may be
implicated in particular conditions to improve the quality
of life.
The effect of vitamin E
on mammary dysplasia: a double-blind study.
London RS, Sundaram GS, Murphy L, Manimekalai S,
Reynolds M, Goldstein PJ.
Obstet Gynecol 1985 Jan;65(1):104-6
Alpha-tocopherol (vitamin E) has been used to treat
patients with benign breast disease. To evaluate the
efficacy of this treatment, a randomized, double-blind
placebo-controlled study was performed on 128 women with
confirmed mammary dysplasia. Patients were treated with
placebo or 150, 300, or 600 IU of d, 1 alpha-tocopherol per
day for two months; breast examinations, sonography, and
thermography were performed in the midluteal phase of the
menstrual cycle before and after treatment. No significant
objective effects to treatment were noted in any of the
parameters monitored. In addition, serum concentrations of
estradiol, progesterone, dehydroepiandrosterone sulfate,
and testosterone were measured before and after treatment.
There were no significant effects on concentrations of
these hormones. From this study, d, 1 alpha-tocopherol does
not seem to be beneficial in the treatment of patients with
mammary dysplasia.
Endocrine parameters
and alpha-tocopherol therapy of patients with mammary
dysplasia.
London RS, Sundaram GS, Schultz M, Nair PP, Goldstein
PJ.
Cancer Res 1981 Sep;41(9 Pt 2):3811-3
Patients with mammary dysplasia (17 patients) and
controls (6 patients) were treated in a double-blind study
with alpha-tocopherol acetate (600 units/day).
Determination of serum alpha-tocopherol, estradiol,
estriol., and progesterone were made from blood samples
collected on Day 21 of the menstrual cycle before and
during therapy. Eight-eight % of patients showed clinical
response to therapy. Serum alpha-tocopherol concentrations
rose after therapy in patients and controls. Serum
estradiol and progesterone concentration were not
statistically different in patients or controls after
therapy, although patients showed a trend toward increased
serum progesterone concentration. However, the ratio of
progesterone to estradiol, which is abnormal in mammary
dysplasia patients, rose from 30 +/- 7 (S.E.) to 53 +/- 11
in patients after alpha-tocopherol therapy (p less than
0.05). Control patients showed no significant change in
progesterone/estradiol ratio. Results of this study
indicate that alpha-tocopherol therapy may correct an
abnormal progesterone/estradiol ratio in patients with
mammary dysplasia, with implications on reducing future
risk for malignant breast disease.
Treatment of breast
fibrocystic disease with tanazol
Lopez S.P.; Martinez E.J.; Reillo M. M. Reillo, Servicio
Obstetricia y Ginecologia, Hospital Marina Baixa,
Villajoyosa, Alicante Spain
Acta Ginecologica (ACTA GINECOL.) (Spain) 1996, 53/10
(304-309)
Purpose: To assess the response of breast fibrocystic
disease treated with tanazol or gestagens. Design:
Retrospective and comparative study on therapy with tanazol
or gestagens. Material and methods: Clinic, echographic,
and mammografic features of breast fibrocystic disease were
analyzed in 119 women. These patients were treated with
tanazol or gestagens over 6 months at least. Conclusions:
Tanazol gets complete improvement of symptoms in 25.2% of
cases; partial improvement in 10.9%, and no improvement in
8.4% of them versus progestagens in 33.6%, 8.4% and 17.7%
respectively. These outcomes were remarkable in patients
with multiple palpable nodes of the breast. There were
significant differences (p = 0.023) in these patients but
no in patients with breast pain.
[Treatment of
fibrocystic breast disease with lisuride] [Article
in Spanish]
Lopez Rosales C, Romero Espinosa RE, Juarez Vazquez J.
Hospital Dr. Dario Fernandez Fierro, ISSSTE, Mexico,
D.F.
Ginecol Obstet Mex 1991 Dec;59:358-61
To study the efficacy of lisuride in fibrocystic
mastopathy, we conducted a clinical trial in 23 out
patients, aged 19-50 years, randomly recruited from the
gynecological service of the ISSSTE, Dr. Dario Fernandez
Fierro. Hospital. The only exclusion criteria was having
received previous treatment. The patients clinical history
was recorded. Physical examination, hormone profile (FSH,
LH, prolactin, testosterone, estrogen and progesterone) and
ultrasound exam of the mammae at baseline were performed in
all patients, as well as, mammography in patients older
than 40 years or those requiring so. Treatment was started
with 1/2 tablet of lisuride (0.1 mg)/8 hours, preferably
with meals, for 3 months. At the end of therapy, hormone
profile, ultrasound of the mammae and physical examination
were repeated for control purposes. We obtained the
following results; fibrocystic mastopathy was most frequent
in women aged 20-29 years, mean age 31 years symptoms
disappeared in 36.9% and were reduced notably in 63.1%, of
cases. Grade O ultrasound lesions disappeared in 100% of
patients and grade I and II lesions improved. On physical
examination all patients showed improvement; estrogen
values were reduced and progesterone incremented. The
prolactin level were normal at baseline, as well as by the
end of treatment. One patient suffered severe side effects
which required interruption of treatment; 4 patients
experimenting light side effects were able to continue
therapy and in the remaining 18 patients, no adverse
reactions were observed.
Mammographic breast
density during hormone replacement therapy: effects of
continuous combination, unopposed transdermal and
low-potency estrogen regimens.
Lundstrom E, Wilczek B, von Palffy Z, Soderqvist G, von
Schoultz B. Department of Obstetrics and Gynecology,
Karolinska Hospital, Stockholm, Sweden.
Climacteric 2001 Mar;4(1):42-8
OBJECTIVE: The aim of this study was to evaluate the
impact of different hormone replacement therapy (HRT)
regimens on mammographic breast density.
STUDY DESIGN: Mammographic density was recorded in women
participating in a population-based screening program. At
first mammogram, all women were non-users of HRT, and
thereafter reported continuous use of the same HRT regimen.
The study population comprised 158 women: a total of 52
women were using continuous combined HRT (conjugated equine
estrogen 0.625 mg plus medroxyprogesterone acetate 5 mg);
51 women were using low-dose oral estrogen alone (estriol 2
mg daily); and 55 women were using unopposed transdermal
estrogen given as a patch (estradiol 50 micrograms/24 h).
Films were coded and analyzed for mammographic density by
an independent radiologist blinded to treatments.
Mammographic density was classified according to Wolfe.
RESULTS: An increase in mammographic density was much
more common among women taking continuous combined HRT
(40%) than for those using oral low-dose estrogen (6%) and
transdermal (2%) treatment. The increase in density was
already apparent at the first visit after starting HRT.
During long-term follow-up, there was very little change in
mammographic status.
CONCLUSION: HRT regimens were shown to have different
effects on the normal breast. There is an urgent need to
clarify the biological nature and significance of a change
in mammographic density during treatment and, in
particular, its relation to symptoms and breast cancer
risk.
Upgrade rate of core
biopsy-determined atypical ductal hyperplasia by open
excisional biopsy.
Maganini RO, Klem DA, Huston BJ, Bruner ES, Jacobs HK.
The Breast Health Center, DuPage Medical Group, 1250 N.
Mill St., Naperville, IL 60563, USA.
Am J Surg 2001 Oct;182(4):355-8
BACKGROUND: Core biopsy finding of atypical ductal
hyperplasia (ADH) are generally followed by open biopsy to
avoid underestimation of malignant disease.
METHODS: Retrospective examination of 11 gauge
stereotactic-guided vacuum-assisted core biopsies was made
with respect to ADH diagnosis, follow-up open biopsy, and
upgrade rate. Readily available clinical, mammographic, and
pathologic features potentially contributory to an upgrade
were studied.
RESULTS: This series of 1,313 patients had 43 ADH
diagnoses. Thirty-two had open follow-up. There were 4
upgrades. Mammographic indication for biopsy, age, removal
of calcifications, and the percentage of ADH in the
specimen were not significant in predicting an upgrade with
all probabilities over 0.10, odds ratios not different than
1, and 95% bounds all encompassing 1.
CONCLUSIONS: These data indicate a high upgrade rate
(13%) for ADH-positive core biopsies with no definitive
predictive criteria for an upgrade. Our data support
follow-up excision of ADH lesions diagnosed by core
biopsy.
N-3 and N-6 fatty acids
in breast adipose tissue and relative risk of breast cancer
in a case-control study in Tours, France.
Maillard V, Bougnoux P, Ferrari P, Jourdan ML, Pinault
M, Lavillonniere F, Body G, Le Floch O, Chajes V.
Laboratoire de Biologie des Tumeurs, Clinique
d'Oncologie-Radiotherapie, Service de
Gynecologie-Obstetrique, E.A. 2103, Unite de Recherche
Associee Universite-INRA, CHU, Tours, France.
Int J Cancer 2002 Mar 1;98(1):78-83
Experimental studies have indicated that n-3 fatty
acids, including alpha-linolenic acid (18:3 n-3) and
long-chain n-3 polyunsaturated fatty acids inhibit mammary
tumor growth and metastasis. Earlier epidemiological
studies have given inconclusive results about a potential
protective effect of dietary n-3 polyunsaturated fatty
acids on breast cancer risk, possibly because of
methodological issues inherent to nutritional epidemiology.
To evaluate the hypothesis that n-3 fatty acids protect
against breast cancer, we examined the fatty acid
composition in adipose tissue from 241 patients with
invasive, nonmetastatic breast carcinoma and from 88
patients with benign breast disease, in a case-control
study in Tours, central France. Fatty acid composition in
breast adipose tissue was used as a qualitative biomarker
of past dietary intake of fatty acids. Biopsies of adipose
tissue were obtained at the time of surgery. Individual
fatty acids were measured as a percentage of total fatty
acids, using capillary gas chromatography. Unconditional
logistic regression modeling was used to obtain odds ratio
estimates while adjusting for age, height, menopausal
status and body mass index. We found inverse associations
between breast cancer-risk and n-3 fatty acid levels in
breast adipose tissue. Women in the highest tertile of
alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39
(95% confidence intervals [CI] = 0.19-0.78) compared to
women in the lowest tertile (trend p = 0.01). In a similar
way, women in the highest tertile of docosahexaenoic acid
(22:6 n-3) had an odds ratio of 0.31 (95% CI = 0.13-0.75)
compared to women in the lowest tertile (trend p = 0.016).
Women in the highest tertile of the long-chain n-3/total
n-6 ratio had an odds ratio of 0.33 (95% confidence
interval = 0.17-0.66) compared to women in the lowest
tertile (trend p = 0.0002). In conclusion, our data based
on fatty acids levels in breast adipose tissue suggest a
protective effect of n-3 fatty acids on breast cancer risk
and support the hypothesis that the balance between n-3 and
n-6 fatty acids plays a role in breast cancer. Copyright
2001 Wiley-Liss, Inc.
Effect of herbal teas
on hepatic drug metabolizing enzymes in rats.
Maliakal PP, Wanwimolruk S. School of Pharmacy,
University of Otago, Dunedin, New Zealand.
J Pharm Pharmacol 2001 Oct;53(10):1323-9
We have investigated the effect of herbal teas
(peppermint, chamomile and dandelion) on the activity of
hepatic phase I and phase II metabolizing enzymes using rat
liver microsomes. Female Wistar rats were divided into six
groups (n = 5 each). Three groups had free access to a tea
solution (2%) while the control group had water. Two groups
received either green tea extract (0.1%) or aqueous
caffeine solution (0.0625%). After four weeks of
pretreatment, different cytochrome P450 (CYP) isoforms and
phase II enzyme activities were determined by incubation of
liver microsomes or cytosol with appropriate substrates.
Activity of CYP1A2 in the liver microsomes of rats
receiving dandelion, peppermint or chamomile tea was
significantly decreased (P < 0.05) to 15%, 24% and 39%
of the control value, respectively. CYP1A2 activity was
significantly increased by pretreatment with caffeine
solution. No alterations were observed in the activities of
CYP2D and CYP3A in any group of the pretreated rats.
Activity of CYP2E in rats receiving dandelion or peppermint
tea was significantly lower than in the control group, 48%
and 60% of the control, respectively. There was a dramatic
increase (244% of control) in the activity of phase II
detoxifying enzyme UDP-glucuronosyl transferase in the
dandelion tea-pretreated group. There was no change in the
activity of glutathione-S-transferase. The results
suggested that, like green and black teas, certain herbal
teas can cause modulation of phase I and phase II drug
metabolizing enzymes.
Effects of
eicosapentaenoic and gamma-linolenic acid on lung
permeability and alveolar macrophage eicosanoid synthesis
in endotoxic rats.
Mancuso P, Whelan J, DeMichele SJ, Snider CC, Guszcza
JA, Claycombe KJ, Smith GT, Gregory TJ, Karlstad MD. Life
Sciences Program in Physiology, University of Tennessee,
USA.
Crit Care Med 1997 Mar;25(3):523-32
OBJECTIVES: Proinflammatory eicosanoids (cyclooxgenase
and lipoxygenase metabolites of arachidonic acid) released
by alveolar macrophages play an important role in
endotoxin-induced acute lung injury. We investigated the
effect of prefeeding rats for 21 days with enteral diets
that provided the anti-inflammatory fatty acids,
eicosapentaenoic acid and gamma-linolenic acid (derived
from fish oil and borage oil, respectively), as compared
with an n-6 fatty acid-enriched diet (corn oil) on the
following: a) lung microvascular protein permeability,
arterial blood pressure, and platelet and white blood cells
in a model of endotoxin-induced acute lung injury; b)
alveolar macrophage prostaglandin and leukotriene
synthesis; and c) liver and alveolar macrophage
phospholipid fatty acid composition.
DESIGN: Prospective, randomized, controlled,
double-blind study.
SETTING: Research laboratory at a university medical
center.
SUBJECTS: Male Long-Evans rats, weighing 250 g.
INTERVENTIONS: Rats were randomized into four dietary
treatment groups and fed nutritionally complete diets (300
kcal/kg/day), containing 55.2% of the total calories from
fat with either 97% corn oil, 20% fish oil, 20% fish and 5%
borage oil, or 20% fish and 20% borage oil for 21 days. On
day 22, lung microvascular protein permeability, mean
arterial pressure, and platelet and white blood cell counts
were determined for 2 hrs after an intravenous injection of
Salmonella enteritidis endotoxin (10 mg/kg). In a second
group of prefed rats, the phospholipid fatty acid
composition was determined in liver and alveolar
macrophages. Alveolar macrophages were harvested by
bronchoalveolar lavage and stimulated in vitro with a
calcium ionophore (A23187), and the concentrations of
leukotrienes B4 and B5, thromboxane A2, prostaglandin E2,
and 6-keto-prostaglandin F1 alpha were measured in a third
group of prefed rats.
MEASUREMENT AND MAIN RESULTS: Lung permeability was
greatest with corn oil and was significantly attenuated
with 20% fish oil and 20% fish and 5% borage oil, and this
effect approached significance with 20% fish and 20% borage
oil (p = .06). The early and late hypotensive effects of
endotoxin were attenuated with 20% fish oil, 20% fish and
5% borage oil, and 20% fish and 20% borage oil, as compared
with corn oil. Concentrations of leukotriene B4,
prostaglandin E2, and thromboxane B2 released from
A23187-stimulated alveolar macrophages were significantly
lower with 20% fish oil and 20% fish and 20% borage oil, as
compared with corn oil. The increase in lung microvascular
protein permeability with 20% fish and 20% borage oil was
not significantly different than the lung microvascular
protein permeability that was found in animals receiving
20% fish oil (p = .20) and 20% fish and 5% borage oil (p =
.31). Alveolar macrophage and liver phospholipid
concentrations of arachidonic acid were lower, and the
concentrations of eicosapentaenoic acid and docosahexaenic
acid were higher, with 20% fish oil, and 5% borage oil, and
20% fish and 20% borage oil, as compared with corn oil.
Dihomo-gamma-linolenic acid, the desaturated and elongated
intermediate of gamma-linolenic acid, was increased with
20% fish and 20% borage oil, as compared with 20% fish oil
and 20% fish and 5% borage oil.
CONCLUSIONS: The severity of pulmonary microvascular
protein permeability and the degree of hypotension were
reduced with fish or fish and borage oil diets, as compared
with corn oil, in endotoxic rats. The reduced synthesis of
the proinflammatory arachidonic acid-derived mediators,
leukotriene B4, thromboxane B2, and prostaglandin E2 from
stimulated alveolar macrophages was indicative of a
decrease in arachidonic acid and an increase in
eicosapentaenoic acid and docosahexaenoic acid in cell
membrane phospholipids.
Effects and
tolerability of n-6 essential fatty acid supplementation in
patients with recurrent breast cysts.
Mansel, R.E., Gateley, C.A., Harrison, B.J. et al.
J. Nutr. Med. 1990a; 1: 195-200.
No abstract available.
A randomized trial of
dietary intervention with essential fatty acids in patients
with categorized cysts.
Mansel RE, Harrison BJ, Melhuish J, Sheridan W, Pye JK,
Pritchard G, Maddox PR, Webster DJ, Hughes LE. University
Department of Surgery, Cardiff, Wales, United Kingdom.
Ann N Y Acad Sci 1990;586:288-94
Two hundred women with breast cysts proven by aspiration
were entered into a randomized double-blind trial of Efamol
(evening primrose oil) at a dose of 6 capsules daily or
equivalent placebo dose for a year. Cysts were categorized
by initial electrolyte composition, and follow-up continued
for 1 year posttherapy. Recurrent cyst formation in the
first year was slightly (but not significantly) lower in
the Efamol group compared with the placebo-treated group.
The Efamol treatment was well tolerated as the dropout rate
was only 7% and equal in both the active and placebo
groups. The initial electrolyte composition did not predict
for cyst recurrence.
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