Professional Documents
Culture Documents
female conditions
David
R.
Seaman,
DC,
MS,
DABCN
Professor,
Clinical
Sciences
Pregnancy
deame@deame.com
NUHS-St
Pete
Speakers Bureau
Clinical Consultant
Multivitamin/mineral
Magnesium (400-1000 mg)
Fish oil (EPA/DHA) (1000-3000 mg)
Vitamin D (2000-10,000 IU)
a-Lipoic acid & acetyl-L-carnitine (ALCAR)
Pregnancy
and
inflammation
Pregnancy = inflammation?
Inflammation is central to reproductive success.
Ovulation, menstruation, implantation, and
parturition are all inflammatory processes.
Components of the immune system (major
histocompatability complex) have been implicated
in mate selection and spontaneous abortion.
An exaggerated inflammatory response (systemic
or localized) is a mechanism of disease in
spontaneous abortion, preterm labor, preterm
prelabor rupture of the membranes (PPROM),
preeclampsia, and other great obstetrical
syndromes.
Romero R et al. Inflammation in pregnancy: its roles in reproductive physiology,
obstetrical complications, and fetal injury. Nutr Rev. Dec, 2007(II):S194-S202
Implantation = inflammation?
Pregnancy = inflammation?
Parturition = inflammation?
Parturition has also been considered a
localized inflammatory process. The
common terminal pathway of parturition
consists of myometrial activation, cervical
ripening (dilatation and effacement), and
membrane/decidual activation.
The molecular cellular components of
inflammation have been proposed to play a
central role in each of the components of
the common terminal pathway of
parturition.
Romero R et al. Inflammation in pregnancy: its roles in reproductive physiology,
obstetrical complications, and fetal injury. Nutr Rev. Dec, 2007(II):S194-S202
Cytokines
IL-6
IL-16
IL-18
colony stimulating factors (CSFs)
macrophage migration inhibitory factor (MIF)
Chemokines
IL-8
monocyte chemotactic protein-1 (MCP-1)
epithelial cell-derived neutrophil-activating peptide
(ENA)-78
regulated on activation normal T cell expressed and
secreted (RANTES)
Romero R et al. Inflammation in pregnancy: its roles in reproductive physiology,
obstetrical complications, and fetal injury. Nutr Rev. Dec, 2007(II):S194-S202
impact on
cardiovascular and
gastrointestinal
disease
Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in the
prevention of ovulatory disorder infertility. Obstet Gynecol. 2007;110(5):1050-58.
Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and
lifestyle in the prevention of ovulatory disorder infertility. Obstet
Gynecol. 2007;110(5):1050-58.
Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in the
prevention of ovulatory disorder infertility. Obstet Gynecol. 2007;110(5):1050-58.
Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in the
prevention of ovulatory disorder infertility. Obstet Gynecol. 2007;110(5):1050-58.
Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in the
prevention of ovulatory disorder infertility. Obstet Gynecol. 2007;110(5):1050-58.
Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in the
prevention of ovulatory disorder infertility. Obstet Gynecol. 2007;110(5):1050-58.
Glycemic index
Glycemic load
Low GI = 55 or less
Low GL = 10 or less
Medium GI = 56 - 69
Medium GL = 11- 19
High GI = 70 or more
High GL = 20 or more
http://www.glycemicindex.com/
http://www.glycemicindex.com/
Zhang C. Dietary fiber intake, dietary glycemic load, and the risk for
Qiu C et al. Dietary fiber intake in early pregnancy and risk of subsequent
preeclampsia. Am J Hypertens. 2008; 21(8): 903-9
Fiber-deficiency states
Diets low in dietary fiber may
underlie or exacerbate
constipation, appendicitis,
hemorrhoids, deep vein
thrombosis, varicose veins,
diverticulitis, hiatal hernia, and
gastroesophageal reflux.
Cordain L et al. Origins and evolution of the Western diet: health implications for the 21st
century. Am J Clin Nutr. 2005; 81(2):341-54
Fiber issues
The fiber content (15.1 g/d) of the typical
US diet is considerably lower than
recommended values (2530 g).
Refined grains contain 400% less fiber
than do whole grains (by energy).
Fiber-rich foods: Fresh fruit typically
contains twice the amount of fiber in whole
grains, and nonstarchy vegetables contain
almost 8 times the amount of fiber in whole
grains on an energy basis.
Cordain L et al. Origins and evolution of the Western diet: health implications for the 21st
century. Am J Clin Nutr. 2005; 81(2):341-54
Nilsen RM, Vollset SE, et al. Folic Acid and Multivitamin Supplement Use and Risk
of Placental Abruption: A Population-based Registry Study. Am J Epidemiol. 2008;
1/10
Wen, Shi Wu, Chen Xi-Kuan, et al. Folic acid supplementation in early second
trimester and the risk of preeclampsia. Am J Obs Gynecol. 2008; 198(1):
45.e1-45.e7.!
10
References
PolycysAc
ovarian
syndrome
Read full text before acting: Cannell JJ, Hollis BW. Use of vitamin D(3) in
clinical practice. Alt Med Rev. 2008;13(1):6-20.
PolycysAc
ovarian
syndrome
PolycysAc
ovaries
have
been
called
oyster
ovaries
because
they
are
enlarged
and
sclerocysAc
with
smooth,
pearl-white
surfaces
w/o
indentaAons.
Many
small
uid-lled
follicle
cysts
lie
beneath
the
thickened
brous
surface
of
the
cortex.
Tzadik M et al. Benign disorders of the ovaries and oviducts. In p.
654-661. In Decherney AH et al. Current Diagnosis and Treatment.
Obstetrics and gynecology. 10th ed. New York: McGraw Hill; 2007
11
PCOS basics:
hap://emedicine.medscape.com/arAcle/256806-workup#a0720
12
PCOS
basics:
ManifestaAons:
persistent
anovulaAon
can
lead
to
enlarged
polycysAc
ovaries,
secondary
amenorrhea
or
oligomenorrhea,
and
inferAlity
Prevalence:
5-10%
with
variances
among
races
and
ethniciAes
50%
of
paAents
are
hirsute
30-75%
are
obese
Most
paAents
with
PCOS
seek
treatment
for
hirsuAsm
or
inferAlity
Multivitamin/mineral
Magnesium
Fish oil (EPA/DHA)
Vitamin D
a-Lipoic acid & acetyl-L-carnitine (ALCAR)
Fiber
Magnesium
Vitamin
D
Chromium
Lipoic
acid
Gymnema
sylvestre
Cinnamon
Vanadium
Not in notes
13
Abstract
Aware of the important benefits of human milk, most U.S. women initiate breastfeeding but difficulties with milk supply
lead some to quit earlier than intended. Yet, the contribution of maternal physiology to lactation difficulties remains poorly
understood. Human milk fat globules, by enveloping cell contents during their secretion into milk, are a rich source of
mammary cell RNA. Here, we pair this non-invasive mRNA source with RNA-sequencing to probe the milk fat layer
transcriptome during three stages of lactation: colostral, transitional, and mature milk production. The resulting
transcriptomes paint an exquisite portrait of human lactation. The resulting transcriptional profiles cluster not by
postpartum day, but by milk Na:K ratio, indicating that women sampled during similar postpartum time frames could be at
markedly different stages of gene expression. Each stage of lactation is characterized by a dynamic range (105-fold) in
transcript abundances not previously observed with microarray technology. We discovered that transcripts for isoferritins
and cathepsins are strikingly abundant during colostrum production, highlighting the potential importance of these
proteins for neonatal health. Two transcripts, encoding b-casein (CSN2) and a-lactalbumin (LALBA), make up 45% of the
total pool of mRNA in mature lactation. Genes significantly expressed across all stages of lactation are associated with
making, modifying, transporting, and packaging milk proteins. Stage-specific transcripts are associated with immune
defense during the colostral stage, up-regulation of the machinery needed for milk protein synthesis during the transitional
stage, and the production of lipids during mature lactation. We observed strong modulation of key genes involved in
lactose synthesis and insulin signaling. In particular, protein tyrosine phosphatase, receptor type, F (PTPRF) may serve as a
biomarker linking insulin resistance with insufficient milk supply. This study provides the methodology and reference data
set to enable future targeted research on the physiological contributors of sub-optimal lactation in humans.
Citation: Lemay DG, Ballard OA, Hughes MA, Morrow AL, Horseman ND, et al. (2013) RNA Sequencing of the Human Milk Fat Layer Transcriptome Reveals
Distinct Gene Expression Profiles at Three Stages of Lactation. PLoS ONE 8(7): e67531. doi:10.1371/journal.pone.0067531
Editor: Kartik Shankar, University of Arkansas for Medical Sciences, United States of America
Received January 7, 2013; Accepted May 20, 2013; Published July 5, 2013
Copyright: ! 2013 Lemay et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by the Cincinnati Childrens Hospital Perinatal Institute (http://www.cincinnatichildrens.org/service/p/perinatal/default/);
Cincinnati Diabetes and Obesity Center (http://diabetes.uc.edu/Research/Overview.aspx); National Center for Research Resources (NCRR) (P51RR000169-49S1); the
National Center for Advancing Translational Sciences (NIH 8 UL1 TR000077-04); and National Institutes of Health (NIH) HD13021. The content is solely the
responsibility of the authors and does not necessarily represent the official views of the NCRR or NIH. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
Introduction
Diabetes Care.
2011;34:1669-75.
Premenstrual syndrome!
Symptoms of PMS
14
EAology
of
PMS
Unknown,
but
the
following
have
been
historically
proposed:
estrogen-progesterone
imbalance,
excess
aldosterone,
hypoglycemia,
hyperprolacAnemia,
psychogenic
factors
Recent
consensus:
physiologic
ovulaAon
is
trigger
(medical
or
surgical
inhibiAon
of
ovulaAon
eliminates
symptoms);
with
estrogen/
progesterone
and
serotonin
being
viewed
as
parAcipants
Decherney
AH,
Goodwin
TM.
Current
diagnosis
&
treatment:
obstetrics
and
gynecology.
10th
ed.
McGraw-Hill:
NY;
2007
Diagnosis
of
PMS
A.
Based
on
paAent
history
B.
Laboratory
TesAng
1.
No
physiological
or
hormonal
tests
conrm
PMS/
PMDD
2.
Laboratory
tests
may
be
in
order
to
rule
out
alternaAve
diagnoses.
-
This
includes
such
condiAons
as
anemia,
autoimmune
disorders,
endocrine
and
thyroid
disorders
(hyperprolacAnemia,
hypothyroidism,
diabetes
mellitus),
chronic
faAgue
syndrome,
endometriosis,
and
psychiatric
disorders
hap://www.medscape.com/viewarAcle/551199_2
Physical
EvaluaAon
A.Vital
signs
B. Weight
C. Thyroid
examinaAon
D.Breast,
abdominal,
and
pelvic
examinaAon
if
indicated
as
part
of
rouAne
reproducAve
health
care
E. AddiAonal
physical
examinaAon
components
as
indicated
by
history
F. Assessment
of
aect
hap://www.medscape.com/viewarAcle/551199_2
SomaAc
-
breast
tenderness
-
abdominal
bloaAng
-
headache
-
swelling
of
extremiAes
15
NON-pharmacologic Rx
Pharmacologic
Rx
A. Non-steroidal
anA-inammatory
drugs
(NSAIDs)
alleviate
most
physical
symptoms.
B. Spironolactone
1.
EecAve
for
breast
tenderness
and
bloaAng
2.
The
recommended
dose
is
50
mg
twice
daily
to
begin
2
to
3
days
before
the
anAcipated
symptoms
unAl
menses.
3.
Potassium
levels
should
be
monitored.
Why?
4.
Avoid
use
in
those
with
impaired
renal
funcAon.
C.
Combined
oral
contracepAves
(COC)
hap://www.medscape.com/viewarAcle/551199_2
5. Liver failure
6. Others
- mechanical ventilation
- post-metabolic acidosis
- psychogenic
Hypoxic causes:
1. Low O2 content
- altitude
- lung disease
- anemia
- CO poisoning
2. Impaired perfusion
- hypovolemia
- septic shock
- cardiogenic shock
Thomson WST et al. Clinical acid-base balance. New York: Oxford U Press; 1997
http://emedicine.medscape.com/article/807277
16
apprehension
faintness
fatigue
headache
impaired concentration
giddiness
irritability
seizure
weakness
visual disturbances
diaphoresis
perioral numbness
dyspnea
1.
2.
palpations
tachycardia
abdominal discomfort
chest pain
air swallowing
breathlessness
yawning and/or sighing
dry mouth
tetany
muscle tightening &
stiffness
distal paresthesias
Mechanism
by which
symptoms
develop?
IMPORTANT #s to embrace!
35-45 mmHg
Thomson WST et al. Clinical acid-base balance. New York: Oxford U Press; 1997
17
Thomson WST et al. Clinical acid-base balance. New York: Oxford U Press; 1997
Thomson WST et al. Clinical acid-base balance. New York: Oxford U Press; 1997
Thomson WST et al. Clinical acid-base balance. New York: Oxford U Press; 1997
light-headedness
impaired intellectual functions
confusion
syncope
seizures
Thomson WST et al. Clinical acid-base balance. New York: Oxford U Press; 1997
18
Thomson WST et al. Clinical acid-base balance. New York: Oxford U Press; 1997
Gastrointestinal
symptoms - such as
nausea, lack of appetite,
and vomitingare all
attributable to cerebral
hypoxia.
Dysmenorrhea!
Dysmenorrhea!
One
of
most
common
complaints
of
gynecologic
paAents
Many
suer
with
mild
discomfort;
dysmenorrhea
is
reserved
for
those
whose
pain
prevents
normal
acAvity
and
requires
medicaAon
Three
types
of
dysmenorrhea:
1. Primary
(no
organic
cause)
2. Secondary
(pathologic
cause)
a.
endometriosis,
adenomyosis,
pelvic
inammatory
disease,
cervical
stenosis,
broids,
and
endometrial
polyps
3. Membranous
(cast
of
endometrial
cavity
she
as
single
enAty
through
undilated
cervix)
4. Cramping
due
to
intrauterine
device
Decherney
AH,
Goodwin
TM.
Current
diagnosis
&
treatment:
obstetrics
and
gynecology.
10th
ed.
McGraw-Hill:
NY;
2007
Prostaglandin
acAvity
Leukotriene
acAvity
Decherney
AH,
Goodwin
TM.
Current
diagnosis
&
treatment:
obstetrics
and
gynecology.
10th
ed.
McGraw-Hill:
NY;
2007:
p.572
hap://emedicine.medscape.com/arAcle/253812
19
Dysmenorrhea
is
OSTEOARTHRITIS
of
the
dysmenorrhea
anatomy
(LA) n-6 FA
(ALA) n-3 FA
Green veg,
chia, flax,
hemp
Fish, n3
meat, wild
game, n3
eggs
GLA
J Am Diet Assoc.
2008;108:1178-1185.
PGE1
TXA1
Anti-inflammatory
2004 Dr. David Seaman.
PGE2
air
gul
Sin
AID
NS
Arachidonic
acid
irin
Asp
DGLA
LTB4
TXA2
Pro-inflammatory
DHA
EPA
Resolvins
Neuroprotectins
Docosatrienes
PGE3 LTB5
TXA3
Anti-inflammatory
Breast
cancer
and
syndrome
X
connecAon
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome
among US adults: findings from the Third National Health and Nutrition
Examination Survey. JAMA 2002;287:3569.
20
Goodwin
PJ
et
al.
Mezormin
in
breast
cancer:
Ame
for
acAon.
J
Clin
Oncol.
2009;27(20):3271-73.
Barclay AW, Petocz P et al. Glycemic index, glycemic load, and chronic disease
risk--a meta-analysis of observational studies. Am J Clin Nutr. 2008; 87(3): 627-37!
21
Cowey S, Hardy RW. The metabolic syndrome: A high-risk state for cancer? Am J
Pathol. 2006; 169(5):1505-22
Cowey S, Hardy RW. The metabolic syndrome: A high-risk state for cancer? Am J
Pathol. 2006; 169(5):1505-22
Cowey S, Hardy RW. The metabolic syndrome: A high-risk state for cancer? Am J
Pathol. 2006; 169(5):1505-22
BRCA
is
a
tumor
suppressor
van der Groep P et al. Pathology of hereditary breast cancer. Cell Oncol. 2011;
34(2): 7188.
22
Allele:
Any of several forms of a gene, usually
arising through mutation, that are
responsible for hereditary variation.
Origin:
193035; < German Allel, apparently as
shortening of German equivalents of
allelomorph or allelomorphic gene;
allelo- < Greek alllo-, combining form
of allln of/to one another, reciprocally
http://efaeducation.nih.gov/sig/eicosa3.html
AA sources:
Grain-fed animals,
(FR tilapia, catfish,
bronzini)
Arachidonic acid
COX/LOX
PGE2, TXA2, LTB4
23
(LA) n-6 FA
(ALA) n-3 FA
Green veg,
chia, flax,
hemp
Fish, n3
meat, wild
game, n3
eggs
GLA
J Am Diet Assoc.
2008;108:1178-1185.
PGE1
TXA1
Anti-inflammatory
2004 Dr. David Seaman.
PGE2
air
gul
Sin
AID
NS
Arachidonic
acid
irin
Asp
DGLA
LTB4
TXA2
Pro-inflammatory
DHA
EPA
Resolvins
Neuroprotectins
Docosatrienes
PGE3 LTB5
TXA3
Anti-inflammatory
24
Erickson
KL,
Hubbard
NE.Faay
acids
and
breast
cancer:
the
role
of
stem
cells.
Prostaglandins
Leukot
Essent
Faay
Acids.
2010;82(4-6):237-41.
Studies
with
animal
models
in
vivo
as
well
as
with
animal
and
human
tumor
cells
in
vitro
suggest
that
specic
faay
acids
could
reduce
breast
tumorigenesis.
The
most
striking
dietary
faay
acid
studies
in
animal
models
that
show
promise
for
reducAon
of
breast
cancer
risk
in
humans
are
with
conjugated
linoleic
acids
(CLA)
and
n-3
faay
acids.
The
specic
target
of
those
faay
acids
is
not
yet
known.
The
isomers,
cis9,
trans11-CLA
and
trans10,
cis12-CLA,
and
the
n-3
faay
acids,
docosahexaenoic
and
eicosapentaenoic,
reduced
the
proliferaAon
of,
and
had
increased
toxicity
towards,
mammary
tumor
iniAaAng
cells.
One
mechanism
involved
in
the
eect
of
n-3
faay
acids
may
be
due
to
alteraAon
of
the
prole
of
prostaglandins.
These
results
indicate
that
select
faay
acids
may
be
useful
for
prevenAng
or
reducing
the
risk
of
breast
cancer
as
they
may
target
the
tumor
iniAaAng
cell.
25
Recent studies have shown that toxicity doesn't occur until the serum level is 200
ng/ml or above.
http://www.grassrootshealth.org/
Clinically,
radionuclide
studies
have
shown
that
breast
atypia
and
malignancy
have
increased
radioacAve
iodine
uptakes.
Imaging
of
the
breasts
in
high-risk
women
has
localized
breast
tumors.
The
potenAal
use
of
breast
iodine
determinaAon
to
determine
estrogen
dependence
of
breast
cancer
has
been
considered
and
the
role
of
iodide
therapy
discussed.
In
conclusion,
iodine
appears
to
be
a
compulsory
element
for
the
breast
Assue
growth
and
development.
It
presents
great
potenAal
for
its
use
in
research
directed
toward
the
prevenAon,
diagnosis,
and
treatment
of
breast
cancer.
32% (23-41)
Food
choices for
Dark chocolate
21%
(14-27)
disease
prevention
Vegetables & Fruit (potatoes) 21%
(14-27)
and health
Garlic (all spices)
25% (21-27)
promotion.
Fish (n-3 meat, chicken, eggs) 14% (8-19)
12.5% (10.5-13.5)
Combine effect
76% (63-84)
Franco OH et al. The Polymeal: a more natural, safer, and probably tastier (than
the Polypill) strategy to reduce cardiovascular disease by more than 75%. BMJ.
2004; 329:1447-50
Iodine
26
Patrick L. Iodine: defiency and therapeutic considerations. Alt Med Rev. 2008;13(2):116-27.
Patrick L. Iodine: defiency and therapeutic considerations. Alt Med Rev. 2008;13(2):116-27.
150 mcg/d
Adults
220 mcg/d
Pregnacy
270 mcg/d
Lactation
27
600 mcg/d
1000 mcg/d
3000 mcg/d
Japan (2)
28
Multivitamin/mineral
Magnesium (400-1000 mg)
Fish oil (EPA/DHA) (1000-3000 mg)
Vitamin D (2000-10,000 IU)
a-Lipoic acid & acetyl-L-carnitine (ALCAR)
Fiber
IntersAAal
cysAsis
29
Klumpp DJ, Rudick CN. Summation model of pelvic pain in interstitial cystitis.
Nature Clin Pract. 2008;5(9):494-500.
coffee
tea
soda
alcoholic beverages
citrus fruits and juices
artificial sweeteners
hot pepper
Klumpp DJ, Rudick CN. Summation model of pelvic pain in interstitial cystitis.
Nature Clin Pract. 2008;5(9):494-500.
Endometriosis
Endometriosis
http://emedicine.medscape.com/article/271899-overview#a0156
Endometriosis
http://emedicine.medscape.com/article/271899-overview#a0156
30
Olive DL,
Schwartz LB.
Endometriosis.
NEJM. 1993;
328:1759-69
Origin
of
estrogen
in
endometrioAc
lesions
31
Origin
of
estrogen
in
endometrioAc
lesions?
COX2
Origin
of
estrogen
in
endometrioAc
lesions?
COX2
32
FibrinolyAc
Balance
M
PL
AS
Fibrin
IN
Thrombin
Fibrinogen
ProteolyAc
Enzymes
Plasminogen
acAvator
(PA)
Plasminogen
Menopause
- 3000 mg pancreatin
- 1800 mg papain
- 720 mg trypsin
- 30 mg chymotrypsin
33
Pfeilschifter J et al. Changes in Proinflammatory Cytokine Activity after Menopause. Endo Rev 2002; 23 (1): 90-119
32% (23-41)
Food
choices for
Dark chocolate
21%
(14-27)
disease
prevention
Vegetables & Fruit (potatoes) 21%
(14-27)
and health
Garlic (all spices)
25% (21-27)
promotion.
Fish (n-3 meat, chicken, eggs) 14% (8-19)
12.5% (10.5-13.5)
Combine effect
76% (63-84)
Franco OH et al. The Polymeal: a more natural, safer, and probably tastier (than
the Polypill) strategy to reduce cardiovascular disease by more than 75%. BMJ.
2004; 329:1447-50
Vaginitis
Multivitamin/mineral
Magnesium (400-1000 mg)
Fish oil (EPA/DHA) (1000-3000 mg)
Vitamin D (2000-10,000 IU)
a-Lipoic acid & acetyl-L-carnitine (ALCAR)
Fiber
34
Recurrent
UTI:
dominant
organisms
are
the
uropathogens,
generally
Escherichia
coli
Recurrent
bacterial
vaginosis:
anaerobic
Gram
negaAve
rods,
Gardnerella
vaginalis
Recurrent
yeast
vaginiAs:
mostly
Candida
albicans
Reid
G,
Bruce
AW.
Urogenital
infecAons
in
women:
can
probioAcs
help?
Postgrad
Med
J.
2003;79:428-32.
35
Vulvovaginal
candidiasis
hap://emedicine.medscape.com/arAcle/257141
hap://emedicine.medscape.com/arAcle/257141
Diabetes
mellitus**
Oral
contracepAve
(OCP)
AnAbioAc
use
Immunodeciency
Tight-ng
undergarments
hap://emedicine.medscape.com/arAcle/797497
36
Complimentary
treatments for
vaginitis
Reid
G,
Bruce
AW.
Urogenital
infecAons
in
women:
can
probioAcs
help?
Postgrad
Med
J.
2003;79:428-32.
37
CD4
T helper cells
TH1
TH2
T-reg
IL-4, 5, 13,
Maintenance
which are
of selfassociated with
tolerance
IGE responses,
and IL-10 which
is anti-inflammatory.
Berger A. Science commentary: Th1 and
Th2 responses: what are they. BMJ 2000;
321: p.424
38
Effect of Vit D3
Th1
decreased number
suppress function
Th2
increase number/function
suppress function
inhibit maturation
inhibit Th1 induction
increase Th2 induction
Self tolerance
IL-10
Self tolerance
IL-10
Probiotics
39
Probiotics
Kaptchuk
TJ
et
al.
Sham
device
v
inert
pill:
randomised
controlled
trial
of
two
placebo
treatments.
BMJ.
2006;
332:391-97
40
1.
Turnbaugh
PJ,
Ley
RE,
Mahowald
MA,
Magrini
V,
Mardis
ER,
Gordon
JI:
An
obesity-
associated
gut
microbiome
with
increased
capacity
for
energy
harvest.
Nature
2006,
44:1027-31.
2.
DeBaise
JK,
Zhang
H,
Crowell
MD,
Krajmalnik-Brown
R,
Decker
GA,
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and
its
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G,
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41
History of probiotics
The
concept
of
probioAcs
probably
dates
back
to
1908,
when
Noble
Prize
winner
Eli
Metchniko
suggested
that
the
long
life
of
Bulgarian
peasants
resulted
from
their
consumpAon
of
fermented
milk
products.
The
term
"probioAc"
was
rst
used
in
1965,
by
Lilly
and
SAllwell
for
describing
substances
secreted
by
one
organism
which
sAmulate
the
growth
of
another.
Marteau
et
al
,
in
2002
dened
them
as
"microbial
preparaAons
or
components
of
microbial
cells
that
have
a
benecial
eect
on
health
and
well
being.
Gupta
V,
Garg
R.
ProbioAcs.
Indian
J
Med
Microbiol.
2009;27(3):202-209.
Mucosal functions
Luminal functions
The
luminal
eects
involve
the
ability
of
the
probioAcs
to
alter
the
biochemical
environment
of
the
lumen:
1.
ProbioAcs
lower
the
gut
pH
and
release
anAbacterial
products
called
bacteriocins,
which
prevent
pathogenic
bacteria
from
binding
to
epithelial
cells.
2.
ProbioAcs
appear
to
alter
gene
expression
in
pathogenic
bacteria
and
reduce
their
virulence.
Sherman
PM,
Ossa
JC,
Johnson-Henry
K.
Unraveling
mechanisms
of
acAon
of
probioAcs.
Nutr
Clin
Pract.
2009;24:10-14.
Submucosal functions
The
submucosal
eects
of
probioAcs
involve
anA-
inammatory
adapAve
immune
responses:
42
1.
Lin
HC.
Small
intesAnal
bacterial
overgrowth:
a
framework
for
understanding
irritable
bowel
syndrome.
J
Am
Med
Assoc.
2004;292:
852-858
2.
Peralta
S,
Coaone
C,
Doveri
T,
Almasio
PL,
Craxi
A.
Small
intesAne
bacterial
overgrowth
and
irritable
bowel
syndrome-related
symptoms:
experience
with
Rifaximin.
World
J
Gastroenterol
2009;
15(21):
2628-31.
In
this
study,
one
subject
skewed
the
results
a
bit
because
he
was
unusually
healthy
and
t
and
had
very
high
counts.
3.
Jimenez
MB.
Treatment
of
irritable
bowel
syndrome
with
probioAcs.
An
eAopathogenic
approach
at
last?
Rev
Esp
Enferm
Dig.
2009;
101(8):553-64.
4.
Packey
CD,
Sartor
RB.
Commensal
bacteria,
tradiAonal
and
opportunisAc
pathogens,
dysbiosis
and
bacterial
killing
in
inammatory
bowel
diseases.
Curr
Opin
Infect
Dis.
2009;
22(3):
292-301.
5.
Hvatum
M,
Kanerud
L,
Hallgren
R,
Brandtzaeg
P.
The
gutjoint
axis:
cross
reacAve
food
anAbodies
in
rheumatoid
arthriAs.
Gut
2006;55:1240-47.
43
44
Fasano A. Zonulin and its reg of intest barrier functionPhys Rev. 2011;91:151-75.
Fasano A. Zonulin and its reg of intest barrier functionPhys Rev. 2011;91:151-75.
Fasano A. Zonulin and its regulation of intestinal barrier function: the biological
door to inflammation, autoimmunity, and cancer. Phys Rev. 2011;91:151-75.
O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO reports. 2006;
7:688-93
45
O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO reports. 2006;
7:688-93
Functions of the
intestinal flora.
O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO reports. 2006;
7:688-93
Safety of probiotics - 1
46
Safety of probiotics - 2
Results:
In
total,
1966
arAcles
were
idenAed,
of
which
72
fullled
the
inclusion
criteria.
There
were
20
case
reports
of
adverse
events
in
32
paAents,
all
of
which
were
infecAons
due
to
Lactobacillus
rhamnosus
GG
or
Saccharomyces
boulardii;
the
risk
factors
included
central
venous
catheters
and
disorders
associated
with
increased
bacterial
translocaAon.
There
were
52
arAcles
reporAng
53
trials
in
which
4131
paAents
received
probioAcs.
Most
trials
showed
either
no
eect
or
a
posiAve
eect
on
outcomes
related
to
safety
(eg,
mortality
and
infecAons).
Only
3
trials
showed
increased
complicaAons,
which
were
largely
noninfecAous
in
nature
and
in
specic
paAent
groups
(eg,
transplant
and
pancreaAAs).
In
2
of
these
trials,
the
probioAc
was
administered
through
a
postpyloric
tube.
Whelan
K,
Myers
CE.
Safety
of
probioAcs
in
paAents
receiving
nutriAonal
support:
a
systemaAc
review
of
case
reports,
randomized
controlled
trials,
and
nonrandomized
trials.
Am
J
Clin
Nutr.
2010;91(3):687-703.
Aragon
G,
Graham
DB,
Borum
M,
Doman
DB.
ProbioAc
therapy
for
irritable
bowel
syndrome.
Gastroenterol
Hepatol.
2010;6(1)39-44.
Packey
CD,
Sartor
RB.
Commensal
bacteria,
tradiAonal
and
opportunisAc
pathogens,
dysbiosis
and
bacterial
killing
in
inammatory
bowel
diseases.
Curr
Opin
Infect
Dis.
2009;
22(3):
292-301.
Beckham
H,
Whitlow
CB.
The
medical
and
nonoperaAve
treatment
of
diverAculiAs.
Clin
Colon
Rectal
Surg.
2009;22(3):156-60.
Lye
HS
Kuan
CY,
Ewe
JA,
Fung
WY,
Liong
MT.
The
improvement
of
hypertension
by
probioAcs:
eects
on
cholesterol,
diabetes,
renin,
and
phytoestrogens.
Int
J
Mol
Sci.
2009:10:3755-75.
Sullivan
A,
Nord
CE,
Evengrd
B.
Eect
of
supplement
with
lacAc-acid
producing
bacteria
on
faAgue
and
physical
acAvity
in
paAents
with
chronic
faAgue
syndrome.
NutriAon
Journal.
2009,
8:4.
Rao
AV
et
al.
A
randomized,
double-blind,
placebo-controlled
pilot
study
of
a
probioAc
in
emoAonal
symptoms
of
chronic
faAgue
syndrome.
Gut
Pathogens.
2009;1:6.
Shanahan
F.
Gut
microbes:
from
bugs
to
drugs.
Am
J
Gastroenterol.
2010;105:275-79.
The
microbiota
is
inuenced
by
diet
and
lifestyle
factors,
and
has
become
a
target
for
drug
therapy
in
various
disorders.
However,
it
also
oers
new
opportuniAes
as
a
repository
of
bioacAves
from
which
novel
drugs
may
be
mined.
47