Ampliando o conceito de saúde - Microbioma - Dra. Maria Emilia Gadelha Serra
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Transcript of Ampliando o conceito de saúde - Microbioma - Dra. Maria Emilia Gadelha Serra
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http://planetasustentavel.abril.com.br/noticia/ambiente/poluicao-ninguem-ve-hormonios-nanomateriais-remedios-poluem-agua-559952.shtml
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O corpo humano adulto
é composto de
60% a 75% de água.
A quantidade de água
varia em função da
idade, sexo e do tecido
adiposo que o indivíduo
possui.
.
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Rappaport SM. Discovering environmental causes of disease.
J Epidemiol Community Health 2012;66:99-102.
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“A new paradigm is needed to assess how a lifetime of exposure to environmental factors affects the risk of developing chronic diseases. Although the risks of developing chronic diseases are attributed to both genetic
and environmental factors, 70 to 90% of disease risks are probably due to differences in environments. Yet, epidemiologists
increasingly use genomewide association studies (GWAS) to investigate diseases, while relying on questionnaires to characterize “environmental exposures”.”
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Capacidade
detoxificante
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O que nos faz adoecer?
Genuis SJ. What’s out there making us sick?
J Environ Public Health. 2012;2012:605137
Toxinas
Deficiências
Germes
Genética
Fatores Psicológicos
Doença
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A teoria dos seis graus de separação originou-se a partir de um estudo científico, que criou a teoria de que, no mundo, são necessários no máximo seis laços de amizade para que duas pessoas quaisquer estejam ligadas.
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www.barabasilab.com
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“Systems biology is the science of discovering, modeling, understanding and ultimately engineering at the molecular level the dynamic relationships between the biological molecules that define living organisms.” – Lee Hood, MD, PhD President and Co-founder, Institute for Systems Biology
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www.systemsbiology.org
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“Why Use Blood as a Window Nanotechnology and microfluidics devices exist that can measure 50 organ-specific blood proteins from each of the 50 organs in just five minutes using only a fraction of a droplet of blood.” See more at: http://www.systemsbiology.org/p4-medicine#sthash.TulKFkNb.dpuf
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A aproximação futura da enfermidade humana precisa ser vista a partir dos sistemas. Do ponto de vista da patobiologia dos sistemas, define-se como uma ciência que integra os aspectos genéticos, genômicos, bioquímicos, celulares, fisiológicos e clínicos para criar uma rede que sirva de modelo para predizer sua expressão e instaurar uma terapêutica individualizada.
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Modelo Terapêutico Integral
Barasi A. Network Medicine: From Obesity to to the Diseasome. N. Engl. J. Med. 357:4 July 2007
Rede Metabólica
Rede de Doenças
Rede Social
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James L. Oschman
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46
James L. Oschman
Três formas de aprisionamento dos materiais tóxicos na
matriz extracelular
a. Aprisionamento mecânico
b. União iônica
c. União relacionada com a hidrofilia
Dr. Aristides de Faria Jr. CRM – 35.849
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Armazenamento de Toxinas
• Em diversos tecidos e órgãos
• Se a afinidade por um órgão for grande, a toxina acumulará ou formar um depósito por anos
• Toxinas insolúveis em gordura permanecem no plasma e fluidos intesticiais
• Contaminantes solúveis em gordura atingem todos os compartimentos e podem acumular no tecido adiposo
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• Algumas toxinas apresentam afinidade
para certos tecidos – Tetraciclina para o osso
– Organoclorados, por ex, DDT e dioxinas para o tecido adiposo
Sanchez-AR, Rogers RS 3rd, Sheridan PJ. Tetracycline and other tetracycline-derivative staining of the teeth
and oral cavity. Int J Dermatol. 2004;43(10):709-715.
Armazenamento de Toxinas
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pH
20 m2
80-120 m2
250-500 m2
Vias de
Detoxificação
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• Cansaço frequente ou queda de energia inexplicada
• Dores musculares espontâneas
• Dificuldade de concentração ou déficits de memória
• Irritabilidade fácil ou mudanças de humor frequentes
• Alterações de sono
• Acordar com a sensação de que não dormiu bem
• Ganho fácil de peso ou sensação de "inchaço" generalizado
• Desconfortos intestinais variados
• Dores de cabeça leves intermitentes
• Nível de saúde incompatível com a idade cronológica
• Queda de cabelo
• Unhas quebradiças
• Infertilidade
• Alterações da libido
Sintomas de Toxicidade Crônica
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Cólicas
Gases
Distensão abdominal
Diarréias
Intolerâncias alimentares
Alergias alimentares
Deficiências nutricionais
Sínd. Intestino Irritável
Colite ulcerativa
Doença de Crohn
Diverticulose
Polipose
Câncer
Infecção urinária
Candididíase vaginal de repetição
Alteração do humor
Depressão
Insônia
Enxaqueca
Obstrução nasal
Rinite
Alergias
Infecções de repetição
Síndrome da Fadiga crônica
(desânimo, estresse, cansaço,
enxaquecas, mau-humor – “enfezada”,
edema nas pernas, desinteresse no
trabalho, perda do apetite sexual,
mãos e pés frios)
Autismo
Leucemia
Halitose
Fibromialgia
Artralgias
Artrite reumatóide
Doenças por imunocomplexos
Osteoporose
Eczema
Dematite atópica
Psoríase
Urticária
Insuficiência venosa crônica
Úlceras de MMII
Tromboembolismo
Asma
Patologia coronariana
Hipercolesterolemia
Esteatose hepática
Cirrose hepática
Hipersensibilidade química
Diabetes
Obesidade
Inflamação crônica
patológica persistente
Disbiose intestinal
Hipotireoidismo
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Constipação
Diarréia
ou
urgência fecal
Fezes normais,
principalmente tipo 4
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m2
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500 m2!
GALT: O intestino é o órgão linfóide
mais potente. Sua estrutura
imunológica alberga 60% das linfócitos
T de todo o sistema imunológico.
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Fígado
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MALT
Mucosa
Associated
Lymphoid
Tissue
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Da orofaringe ao intestino encontram-se estruturas linfáticas (gânglios linfáticos solitários, placas de Peyer) afins às de outros âmbitos mucosos (vias respiratórias, urogenitais, etc.)
O MALT é um sistema funcional
caracterizado pela troca integrada
de células e moléculas entre todas as
superfícies mucosas do organismo.
Mucosa
Associated
Lymphoid
Tissue
MALT
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Wershil B.K; Furuta G, MD. Gastrointestinal mucosal immunity.
Journal of Allergy and Clinical Immunology - Volume 121,
Issue 2 Suppl (February 2008)
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TLR-2-4
CD3
CD3
CD25
CD3
CD20
CD10
Pro
gre
sió
n
Resu
ltad
o
LTCD4 Th1
R/. Inmune Celular
R/. Inmune Humoral
LTCD8c
CD28+
TNF-
LT
IL-2
IFN-
IFN-
Activacion
Macrofagos
ROS
NO-
Fr
Y Y
Y Y
Autoinmunidad B IgG –Autoanticuerpos
ANAS – ANCAS -ENAS– A-CCP3 – DNAds
Anti-Mielina, Anti-rACh
LBCD19
Lisis Complemento
Inmunocomplejos
ADCC
Anti-Receptor
Th3
LTCD4
Reg
FoxP3+
IFN-
IL-10
TGF-
ß
LTCD4 IL-17
IL-10
Y Y
LB1
CD19+CD5+
Y
Y
LTCD8s
CD28-
TGF-
ß
IFN-ß
IL-10
IL-4
Tsup Th-10
?
- -
+
+
+
+
+ +
-
-
+
+
IL-6
TGF-β
+
Th-17
IL-1
IL-23
IRF-4
Alergias
IgE
IgM
IgG
IgA
Treg
CD8+CD122+
NK CD16+
CD56+
LTCD
4
NKU
CD16+CD9
+
IL-5
IL-7
IFN-
Tumores Bacterias
Parásitos
Hongos
HLA-DR CD64
CD8 TReg
Th-4?
INMUGEN CORPORATION
Abortos
CD20
IgG2a -
ADCC
Leptina
Resistina
Adiponectina
CD3
Virus
NKT
CD16+
CD56+
-
LTCD4
IL-6
Th2
Th-23
IL-4
IL-5
IL-6
IL-10
IL-13
IL-5 Eosinofilia
-
APC
GM-CSF
M-CSF
Inmugen Corporation . Cra 45 A No. 103B-52. Boota Colombia. Tel: 7049872.
Intolerancia
Alimentaria
IgA
IgG2b/IgG4a
Autoinmunidad T MS, ELA, mielitis, GB,
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Respiratory
tract
SISTEMA IMUNE - MALT COLONIZAÇÃO BACTERIANA
Será coincidência?!...
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http://www.bioxplorer.com/wp-content/uploads/2013/10/human-microbiome-project.jpg
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Sinergia Microbiana
Defesa contra infecção é devida à interação de muitas espécies bacterianas (e leveduras, helmintos,
protozoários e vírus).
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SP 007-0002 01 08.10.2007
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MALT
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Estima-se que 50-60% do sistema linfóide
se localize na submucosa intestinal.
O GALT produz cerca de 60% das
Imunoglobulinas.
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Aprox. 1.000.000.000.000
1012 células
humanas
Aprox.
100.000.000.000.000
1014 bactérias
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6 bilhões de seres humanos = bactérias presentes na palma da mão!
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3-5%
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D 005-0114 11 06.08.2004
“Superorganismo
humano-microbiota”
Células
Bactérias
+
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Até 2 anos para
recompor a microbiota
após curso de
antibioticoterapia de
apenas 7 dias !!!!
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Unborn Babies Soaked in Chemicals,
Survey Finds
July 14, 2005 — By Maggie Fox, Reuters
WASHINGTON — Unborn U.S. babies are soaking in a stew of chemicals, including
mercury, gasoline byproducts and pesticides, according to a report to be released
Thursday. Although the effects on the babies are not clear, the survey prompted
several members of Congress to press for legislation that would strengthen controls
on chemicals in the environment.
The report by the Environmental Working Group is based on tests of 10 samples of
umbilical cord blood taken by the American Red Cross. They found an average of 287
contaminants in the blood, including mercury, fire retardants, pesticides and the
Teflon chemical PFOA. “These 10 newborn babies ... were born polluted," said New
York Rep. Louise Slaughter, who planned to publicize the findings at a news
conference Thursday.
"If ever we had proof that our nation's pollution laws aren't working, it's reading the
list of industrial chemicals in the bodies of babies who have not yet lived outside the
womb," Slaughter, a Democrat, said.
Cord blood reflects what the mother passes to the baby through the placenta.
"Of the 287 chemicals we detected in umbilical cord blood, we know that 180 cause
cancer in humans or animals, 217 are toxic to the brain and nervous system, and 208
cause birth defects or abnormal development in animal tests," the report said.
Blood tests did not show how the chemicals got into the mothers' bodies.
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Transmissão de Toxinas pela Placenta
Dos 117 individuais poluentes
orgânicos persistentes ou metais
analisados, 46 puderam ser
detectados em mais de metade das
placentas. Além disso,
diclorodifenildicloroetileno (p, p'-
DDE) foi encontrado em todas as
placentas. Os dados indicam que a
exposição fetal a dioxinas e furanos
(PCDD / Fs), bifenilas policloradas
(PCBs), p, p'-DDE, e metilmercúrio
depende de paridade da mãe, e
idade.
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Clostridium
cavidades
amálgamas – metais pesados
microssistema
risco de doenças ( AVC, doença cardíaca, diabetes, partos prematuros)
Dentes
Focos dentários
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Corte histológico de placa bacteriana com
colônias de bactérias protegidas (setas) Placa bacteriana
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THE HUMAN BODY - AN OPEN ECOSYSTEM
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Lâmpada fluorescente
22 mg de Hg
Amálgama dentário (cada)
1.000 mg de Hg
www.iaomt.org
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Pesticidas
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PRESENÇA DE BACTÉRIAS NOS
TÚBULOS DENTINÁRIOS
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TRABALHO DO Dr. GEORGE MEINIG - USA
Paciente com alterações
oculares há mais de 5 anos, olho
direito mais comprometido
34 e 35
endodonticamente
tratados sem lesão
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TRABALHO DO Dr. GEORGE MEINIG - USA
48 h após inoculação da cultura das bactérias colhida dos dentes
72 h: olho direito comprometido
Remoção dos dentes com canal: em 72 h paciente sem
lesão ocular e sem recidiva, com controle 3 anos
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Intestinal responses to gut flora during homeostasis (healthy intestine) and IBD. M. Nedim Ince, MD & David E. Elliott, MD. Immunologic and Molecular Mechanisms in Inflammatory Bowel Disease.
Surgical Clinics of North America - Volume 87, Issue 3, June 2007
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Sistema MALT
Pele (SALT)
(UALT)
Nariz (NALT)
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Colite Ulcerativa
Manifestações
Extra-intestinais
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Nedim M, Elliot D. Immunologic and Molecular Mechanisms in Inflammatory
Bowel Disease Surgical Clinics of North America - Volume 87, Issue 3 (June 2007)
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SARTOR, R. B. Role of the enteric microflora in the pathogenesis of intestinal
inflammation and arthritis. Alimentary Pharmacology and Therapeutics. Volume 11
Supplement 3 December 1997 pp 17-23
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The role of small intestinal bacterial
overgrowth, intestinal permeability,
endotoxemia, and tumor necrosis
factor alpha in the pathogenesis of
non-alcoholic steatohepatitis.
Wigg AJ, Roberts-Thomson IC,
Dymock RB, et al.
Gut 2001; 48:206–11
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Microecologia intestinal
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http://www.ncbi.nlm.nih.gov/pubmed/21475195
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http://pt.slideshare.net/ctorgan/microbiome-sport
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http://pt.slideshare.net/ctorgan/microbiome-sport
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http://pt.slideshare.net/ctorgan/microbiome-sport
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http://pt.slideshare.net/ctorgan/microbiome-sport
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http://pt.slideshare.net/ctorgan/microbiome-sport
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Julho 2000
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A verdadeira prevenção começa muito antes da concepção.
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Maria Emilia Gadelha Serra
São Paulo - Brasil
+ 55 11 3078-6777