Escolar Documentos
Profissional Documentos
Cultura Documentos
Mercury
o 5 fases de desenvolvimento
o Embrionária
o Fetal
o Infância
o Fase reprodutiva
o Senescência
o Formação da barreira
hematoencefálica
o Até os 6 meses de idade
(GRANDJEAN & LANDRIGAN, 2006) 4
INTRODUÇÃO
Oxidação Metilação
o Fontes
o Naturais
o Vulcões
o Solos ricos
o Incêndios
o Antropogênicas
o Termoelétricas
o Queimadas
o Aterros sanitários
o Uso e descarte irregulares (garimpo)
(PSU ECOMERGE, 2015; FARELLA et al., 2006; WHO, 2007; ROULET et al., 1998, 1999, 2000a, 2000b) 8
INTRODUÇÃO
• PARESTESIA DISTAL
ATÉ 30 ANOS APÓS
O FIM DA EXPOSIÇÃO
o Iraque
Graves sintomas, muitas vezes fatais
o Guatemala
o Paquistão
Surtos de contaminação via dejetos
industriais e grãos contaminados por
fungicidas Grão cobertos
com fungicida a
Farinha contaminada (pão) base de Hg
o Ilhas Faroé
Déficit cognitivo, entre outros
Alimentação à base de peixe o Nova Zelândia
(EKINO et al., 2007; RUSTAM; HAMDI, 1974; ORDÓÑEZ et al., 1966; SKERFVING; COPPLESTONE, 1976; GRANDJEAN et al., 2010; AXELRAD et al., 2007) 10
INTRODUÇÃO
a dose;
Efeitos
a idade ou estágio de desenvolvimento da pessoa exposta (o feto é mais
variam suscetível);
com
a duração da exposição;
(WHO, 2017) 11
INTRODUÇÃO
Estresso oxidativo
Inflamação
Genotóxicos e epigenéticos
(SPILLER, 2018; GROTTO et al., 2011; OULHOTE et al., 2017; ALGARVE et al., 2013; KHAN et al., 2017) 12
INTRODUÇÃO
o Óleo de peixe
o Protege o cérebro, rim, fígado e coração
• Efeito antiinflamatório
(HACON et al., 2008; BOISCHIO; BARBOSA, 1993; PASSOS et al., 2007; BRASIL et al., 2017; GROTTO et al., 2011) 15
INTRODUÇÃO
o No município de Maués, AM
o Alto consumo de peixe (1-2x ao dia)
o Alto nível de longevidade
o Boa aptidão funcional, equilíbrio e motora
o Baixa incidência de DCNT associado ao guaraná
(LEMIRE et al., 2010, 2011; COSTA KREWER et al., 2011; ANTONINI et al. 2016; RIBEIRO et al., 2013; MAIA-RIBEIRO et al., 2013) 16
INTRODUÇÃO
MANÁUS Maués
AM PA
MT
(BARBIERI & GARDON,
17
2009)
INTRODUÇÃO
Maués
(SANTOS, 2002) 18
INTRODUÇÃO
(BJÖRKLUND et al., 2007; ENGIN et al., 2017; RAND et al., 2012; SMITH & ATROCH, 2007) 19
INTRODUÇÃO
o Guaraná é habitualmente consumido pelos ribeirinhos
o Antioxidante;
o Antitumor;
o Antissenescência;
o Hipolipemiante;
o Anti-inflamatório;
o Antifadiga;
o Melhora da performance cognitiva.
(BITTENCOURT et al. 2013; CADONÁ et al. 2016, 2017; MACHADO et al. 2015; SULEIMAN et al. 2016; KREWER et al. 2014; de OLIVEIRA et al. 20
2011; LEITE et al. 2011, 2013; BONADIMAN et al. 2017; ARANTES et al. 2016)
INTRODUÇÃO
(FENG et al., 2016; ISHIHARA et al., 2016; JEBBETT et al., 2013; OHKUBO; MIYAMOTO; SHIRAISHI, 2016; TOIMELA; TÄHTI, 2004; UNOKI et al., 2016; ATCC, 2018) 21
INTRODUÇÃO
Período Pré-imaginal
Metamorfose ao
corpo adulto
1º
desenvolve-se a
Estágio
partir de células-
tronco
(Discos Imaginais)
2º Estágio
3º Estágio
(MORATA, 1993; REGULSKI et al., 1987; ALBERTS et al, 2002) 23
INTRODUÇÃO
Clivagem
o Utilizado para avaliar Metamorfose Tempo após a
Blastoderma
fertilização*
neurotoxicidade e parâmetros 9
0 sincicial
60 Gema
comportamentais e funcionais, como o Pupa Núcleo
120 Estágios
Minutos*
sono e a locomoção 3-4
Dias*
180 Gastrulação
o Processos celulares fundamentais e Horas*
10 Embrião
mecanismo de desenvolvimento
Larva
conservados 24
Estágio 13
3º estágio
• Aproximadamente 75% dos genes Eclosão
humanos relacionados a doenças têm
homologia funcional com a mosca 2º estágio
1º estágio
* Incubando à 25°C
o Objetivos Gerais
o Realizar ou estudo translacional determinando o efeito da exposição ao
MeHg no ritmo circadiano da mosca-das-frutas D. melanogaster e o efeito
neuroprotetor do guaraná tanto nas alterações comportamentais e
neurotóxicas induzidas pela exposição ao MeHg nas moscas-das-frutas e em
células de neurais SH-SY5Y. Ainda, realizar um estudo transversal para avaliar
se o consumo de guaraná estaria protegendo uma população idosa
ribeirinha amazônica.
25
OBJETIVOS
o Objetivos Específicos
o Avaliar o efeito da exposição preimaginal de D. melanogaster ao MeHg
através da ocorrência de distúrbios neuromusculares e no sono-vigília
presentes na progênie de D. melanogaster obtida pela exposição parental
ou preimaginal ao MeHg;
26
RESULTADOS
RESEARCH ARTICLE
10 10
Parental and preimaginal exposure to methylmercury disrupts locomotor activity and circadian rhythm of adult Drosophila melanogaster. Algarve et al., 2018. 28
RESULTADOS E DISCUSSÃO – ARTIGO 1
Figure 2. Egg-adult viability and egg
production in parental and preimaginal
exposure to MeHg. (A) Egg-adult
viability in 24 h of parental exposure
model. MeHg significantly decreased
the viability of flies from 9µM onward
when parents were previously exposed
to this toxicant during 24 h before
laying eggs. (B) Egg-viability in MeHg
preimaginal exposure. MeHg has a
significant impact on viability from 6 µM
onward. (C) Total egg production in
A B parental MeHg exposure and (D) Total
egg production in preimaginal
exposure. Results showed that no
difference was found compared to the
control group in each treatment.
Different letters indicate significant
differences (p ≤ 0.05) by one-way
analysis of variance followed by Tukey’s
post hoc test. Data are presented as
mean ± SEM.
C D
29
RESULTADOS E DISCUSSÃO – ARTIGO 1
M e H g P a re n ta l E x p o s u re Figure 3. Climbing ability assay of flies from
100 parental and preimaginal exposure. (A) Climbing
5 scheme. Flies were placed into a vertical vial (70 x
C lim b i n g p e r c e n t il e d is t r ib u t io n
80
25
50
10 mm), 5 flies per well, 40 per treatment and
75
95
repetition. Flies were simultaneously dropped and, 5 s
60
after this, a picture was taken. (B) Climbing percentile
distribution in parental exposure showed a dose-
40
response decrease in the 75th percentile. (C) Climbing
percentile distribution in preimaginal exposure
20
showed a dose-response decrease in the 50th
percentile (median value). (D) Parental and
0
0 3 6 9 12 preimaginal climbing ability response. Parental
A B exposed flies are represented as the 75th percentile
M e H g (µ M )
M e H g P a re n ta l E x p o s u re
(flies that were able to climb ≥ 6 cm) while
100
M e H g P r e im a g in a l e x p o s u r e P a re n ta l E x p o s u re P r e im a g in a l E x p o s u r e
preimaginal exposed flies are shown as the 50th
80 5
( > 6 cm ) ( > 5 cm ) percentile (flies that were able to climb ≥ 5cm, the
C lim b i n g p e r c e n t il e d is t r ib u t io n
80
25
median value). MeHg was able to significantly
50 40
C lim b i n g p e r c e n t il e d is t r ib u t io n
a
75 C lim b in g d is t r ib u t io n ( % ) a
decrease the climbing performance when flies were
60 95
60 b parentally-exposed and, also, significantly reduced
30
c c b b the locomotor activity of flies exposed in the
40
40
d
preimaginal period. Different letters indicate
20
c
significant differences (p ≤ 0.05) by Kruskal Wallis
2 02 0 analysis followed by Qui-square test and percentile
10
d distribution. Data are presented as median values or
0
0 0 3 6 9 12
percentiles.
0
0 3 6 9 12
0 3 6 9 12 0 3 6 9 12
C D
M e H g (µ M )
M e H g (µ M )
M e H g (µ M ) M e H g (µ M )
30
RESULTADOS E DISCUSSÃO – ARTIGO 1
Control 3 µM Control 9 µM
30 30
Sleep (min / 30min)
20 20
15 15
10 10
5 5
0 0
A 0 12 24 36 48 60 72 C 0 12 24 36 48 60 72
Control 6 µM Control 12 µM
30 30
25 25
20 20
15 15
10 10
5 5
0 0
B 0 12 24 36 48 60 72 D 0 12 24 36 48 60 72
Figure 4. Circadian rhythm in preimaginal exposed flies to MeHg. Sleep pattern during 72h has statistically changed by MeHg exposure. (A) 3 µM
(B) 6 µM (C) 9 µM and (D) 12 µM. White and black bars above the horizontal axis indicate light and dark cycles, respectively. Considering the whole
72h data analysis, at 6 and 9 µM was observed a significant increase in sleep time compared to the control group (p < 0.0001). When divided into
day periods, the nighttime period (black bars) from 6 µM onward (p < 0.0001) was shown a significant increase in sleep time compared to the
control. Statistical analysis was performed by Friedman test followed by Dunn’s post hoc test. Data are presented as mean ± SEM. 31
Average of 3 days
35
RESULTADOS E DISCUSSÃO – ARTIGO 1
30
25
Sleep (min/30 min)
20
15
10
0
B C
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Time (h)
Control 3 µM 6 µM 9 µM 12 µM
A
Figure 5. Daily circadian rhythm, 3 days average analysis from flies
exposed to MeHg in the preimaginal period. (A) Sleep behavior 3 days
average. Boxes represented areas with a clear difference between
treatments and control group. (B) Sleep mean time from 2 to 7h showed a
significant decrease in sleep time compared to the control group. (C) Sleep
mean time from 18.5 to 24h showed a significant increase in sleep time
compared to control group. Asterisks indicate significant differences (p ≤
0.05) compared to the control group by two-way analysis of variance
followed by Tukey’s post hoc test. Data are presented as mean ± SEM. *p
B
≤ 0.05, **p < 0.01, ***p < 0.001. C
32
Both results deserve to be discussed more in depth.
RESULTADOS E DISCUSSÃO –and 2 mg/kg
ARTIGO 1
effects (WHO
Table 1. Comparison of nighttime sleep time/30 minutes of Drosophila reared that exposur
in the preimaginal period at different MeHg concentrations.
present in fo
MeHg (mM)
et al. 2001,
Statistics Control 3 6 9 12 Therefore, hu
Nighttime 22! above
Mean ± SE 17.70 ± 0.68 18.49 ± 0.77 20.13 ± 0.76 20.94 ± 0.59 19.97 ± 0.62
Median 18.11a 19.75a 20.95b 20.89b 19.70b 0.7 –0.927 mg.
Minimum 6.000 5.500 5.969 12.22 6.125 (nothing else
Maximum 27.31 27.69 29.69 29.78 28.72
Lower 95% CI 16.34 16.94 18.61 19.77 18.74
larly exposed
Upper 95% CI 19.06 20.03 21.64 22.12 21.20 ingestion of
25% Percentile 13.02 12.69 13.79 16.70 16.45 Castro et al.
75% Percentile 23.20 24.64 25.55 25.45 24.00
mentioned a
SE: standard error; CI: confidence interval.
Different letters indicate significant differences (p # 0.05) by Friedman test toxic concen
followed by Dunn's post hoc test. cies, some c
33
RESULTADOS E DISCUSSÃO – ARTIGO 1
A B
Figure 6. Uninterrupted activity for 30 minutes (UA30) and uninterrupted sleep for 30 minutes (US30) of flies
exposed in the preimaginal period to MeHg. (A) UA30 in preimaginal exposure to MeHg significantly
decreased compared to MeHg and the impact of MeHg was more intense during the nighttime. (B) US30
decreased in the daytime and increased in the nighttime period from 6 to 12 µM. Different letters indicate
significant differences (p ≤ 0.05) by one-way analysis of variance followed by Tukey’s post hoc test. Data are
presented as mean ± SEM.
34
RESULTADOS E DISCUSSÃO – ARTIGO 1
0 12 0 12 0 ZT (h) 0 12 0 12 0 ZT (h)
Actogramas do 30 60 Actogramas da
Control
Control
20 40
Sono 10
0
20
0
Atividade
30 60
20
10
40
20
Supplemental material 1.
0 0
Actograms of 72h sleep
A 0 12 0 12 0 ZT (h) F 0 12 0 12 0 ZT (h) and activity data from 32
30
20
60
40
flies developed with or
without MeHg medium (0-
3 µM
3 µM
10 20
0 0
30 60
12 µM), showing the sleep
20
10
40
20
disruption along the days
and the decrease of
B G
0 0
6 µM
6 µM
10 20
0 0 activity actograms. (A and
30
20
60
40
F) Control; (B and G) 3
10 20 µM; (C and H) 6 µM; (D
C 0
H 0
and I) 9 µM and (E and J)
0 12 0 12 0 ZT (h) 0 12 0 12 0 ZT (h) 12 µM. White and black
30 60
20 40 bars above the horizontal
9 µM
9 µM
10 20
0 0 axis indicate light and
30
20
60
40
dark cycles, respectively.
10 20 Sleep data are
D 0
I 0
represented as time
0 12 0 12 0 ZT (h) 0 12 0 12 0 ZT (h) (min/30 min), and activity
30 60 data are represented as
12 µM
12 µM
20 40
10 20 activity counts/30 min.
0
30
0
60
Data are presented as
20 40 mean values.
10 20
0 0
E J 35
ARTIGO 2
Thaís Doeler Algarve, Charles Elias Assmann, Francine Carla Cadoná, Alencar Kolinski Machado, Maria
Fernanda Manica-Cattani, Yukiko Sato-Miyata, Tsunaki Asano, Marta Maria Medeiros Frescura Duarte,
Euler Esteves Ribeiro, Toshiro Aigaki, Ivana Beatrice Mânica da Cruz
36
ARTIGO 2
10 ♂
10 10
Moscas adultas expostas 24h Moscas ovipositando 8h em novo Ovos até o nascimento Moscas adultas para as
em meio padrão com 9µM MeHg meio com 9µM MeHg e Guaraná avaliações, mantidas em meio
e Guaraná (0, 1, 5, 10 e 20mg/mL)* (0, 1, 5, 10 e 20mg/mL)* padrão, sem tratamento
37
ARTIGO 2
Meio DMEM/F12
10% soro fetal bovino Células SH-SY5Y
1% penicilina/estreptomicina
37 ºC
MeHg e/ou
Umedecida Expostas 72h
Guaraná
5 % CO2 e 95% de O2
Avaliações de viabilidade,
formação de colônias,
citocinas inflamatórias, ...
38
RESULTADOS E DISCUSSÃO – ARTIGO 2
a b
Fig. 1 Egg-adult viability of Drosophila melanogaster treated with different guarana concentrations and
MeHg. (a) Viability of flies developed in cultures supplemented with guarana at different concentrations (0-
20 mg/mL); (b) Viability of flies developed in cultures supplemented with guarana at different concentrations
(1-20 mg/mL) plus 9 µM MeHg. Different letters indicated significant differences (p ≤ 0.05) by one-way
analysis of variance followed by Tukey’s post hoc test. Data are presented as mean ± SEM.
39
RESULTADOS E DISCUSSÃO – ARTIGO 2
c
Fig. 2 Climbing assay of flies developed in medium with MeHg
(9 µM) plus guarana concentrations (1-20 mg/mL). (a) Female
percentile distribution of climbing height values. (b) Male
percentile distribution of climbing height values. (c) Frequency
b (%) comparison of fruit flies that climbed > 50 mm among
different treatments. Different letters indicated significant
differences (p ≤ 0.05) by Chi-square statistical analysis.
40
RESULTADOS
Control 9µM MeHg
30 Control 9µM MeHg
30
25
25
mg/mL) and 9 µM MeHg plus guarana, under 12h light/dark 15 cycles. White 15
Boxes - light cycle; Grey boxes – dark cycle; Control group10 in black and 10 9 µM de MeHg
treatments in red lines. Statistical analysis was performed by Friedman test
5
5
followed by Dunn’s post hoc test. Data are presented as mean0 ±0 SEM. 12 24 36
0
48 60 72
0 12 24 36 48 60 72
Time (h)
Time (h)
Control Gua1 Control HgGua1
30 30 Control Gua1 Control HgGua1
30 30
25 25
25
10
10
10
10 + Gua 1 mg/mL
5 5
5 5
0 0
0 0
0 12 24 36 48 60 72 0 12 24 36 48 60 72
0 12 24 36 48 60 72 0 12 24 36 48 60 72
25
10
15
10 10
15
+ Gua 10 mg/mL
10
5 5
5 5
0 0
0 0
0 12 24 36 48 60 72 0 12 24 36 48 60 72
0 12 24 36 48 60 72 0 12 24 36 48 60 72
Time (h) Control Gua20 Time (h)
30 Time (h) 30 Control Gua20 Control HgGua20 Time (h)
30 Control HgGua20
30
25
25 25
Sleep (min / 30min)
9 µM de MeHg
25
Sleep (min / 30min)
Gua 20 mg/mL 15
15 15
15 + Gua 20 mg/mL
10
10 10
10
5
5 5
5
0
0 0
0 12 24 36 48 60 72 0
0 12 24 36 0 48 12 60 24 72 36 48 60 72
Time (h)
0 12 24 36 48 60
4172
Time (h) Time (h)
Time (h)
RESULTADOS E DISCUSSÃO – ARTIGO 2
a c b e d
b e d f
Fig. 4 Sleep behavior analysis of flies reared in guarana (1-20 mg/mL) and MeHg (9 µM) associated with guarana. US30 (a and b), UA30 (c
and d) and total sleep time (e and f) show a guarana impact on sleep behavior and its effect on MeHg sleep disruption pattern. US30
(uninterrupted sleep for 30 min), UA30 (uninterrupted activity for 30 min). Different letters indicated significant differences (p ≤ 0.05) by
one-way analysis of variance followed by Tukey’s post hoc test. Data are presented as mean ± SEM. 42
RESULTADOS E DISCUSSÃO – ARTIGO 2
a b
Fig. 5 Guarana cytoprotective effects on SH-SY5Y
human neural cells culture exposed to MeHg and
guarana for 72 h. (a) Effect of MeHg exposure at
different concentrations (0.03-9 µM); (b) Effect of
guarana exposure at different concentrations (50-1000
µg/mL); (c) Effect of MeHg (6 µM) exposure plus
guarana (100 µg/mL); MTT: mitochondrial metabolic
activity/cell viability. PG: cellular damage/mortality.
Different letters indicate significant differences (p ≤
0.05) by one-way or two-way analysis of variance
followed by Tukey’s post hoc test. Data are presented as
c mean ± SEM.
43
RESULTADOS E DISCUSSÃO – ARTIGO 2
Control MeHg
Fig. 6 Clonogenic assay performed in SHSY-5Y
neural cells exposed to 3 µM MeHg, 100 µg/mL
guarana and 3 µM MeHg plus 100 µg/mL guarana
for 7 days. Different letters indicate significant
differences (p ≤ 0.05) by one-way or two-way
analysis of variance followed by Tukey’s post hoc test.
Data are presented as mean ± SEM.
MeHg+Guarana Guarana
o Coleta de sangue
Maués
o Entrevista estruturada
o Indicadores de saúde
Frequência Percentual
homem 248 45,9
mulher 292 54,1
PA Total 540 100
AM
Média SD
Idade 72,30 7,866
Idade Média SD
MT Homem 72,90 7,442
Mulher 71,79 8,184
45
RESULTADOS E DISCUSSÃO – ARTIGO 3
Table 2. Logistic regression to determine the influence of
biological and health indicator factors in the association
between higher levels of Hg, Se and 8-year riverine elderly
Table 1. Descriptive statistic of Hg, Se and Se/Hg ratio mortality.
Desvio Percentis Wald Risco 95% I.C. do Risco p
Média Padrão Mínimo Máximo 25º 50º (Mediana) 75º Relacionado
Hg (µg/g) 0.011 0.002 0.006 0.015 0.010 0.011 0.012 ao Hg
Idade 78.896 211.321 64.851-688.610 < 0.0001
Se (µg/g) 0.150 0.014 0.128 0.194 0.141 0.147 0.159
Sexo 29.053 0.037 0.011-0.123 < 0.0001
Se/Hg 14627 3045 8.80 22.67 12250 13846 17111 TBARS 0.844 1.020 0.977-1.065 0.358
AOPP 0.144 0.997 0.980-1.014 0.705
NOx 3.999 0.980 0.960-0.999 0.045
HAS 4.081 0.467 0.223-0.977 0.043
DCV 0.019 1.098 0.292-4.136 0.890
Colesterol 2.590 1.006 0.999-1.013 0.107
Constante 6.696 0.084 0.010
Relacionado
ao Se
Idade 0.233 1.131 0.686-1.867 0.629
Sexo 52.725 0.165 0.102-0.269 < 0.0001
TBARS 7.124 0.967 0.942-0.991 0.008
AOPP 2.698 1.008 0.998-1.018 0.100
NOx 5.907 0.987 0.977-0.997 0.015
HAS 7.053 1.862 1.177-2.945 0.008
DCV 0.859 0.647 0.257-1.625 0.354
Colesterol 0.016 1.0003 0.996-1.005 0.899
Constante 3.865 3.167 0.049
46
RESULTADOS E DISCUSSÃO – ARTIGO 3
Healthy Elderlies
Figure 2. General model to understand the effects of Hg and Se in health maintenance and they level in elderly
with a diagnosed disease. Data are presented as mean +/- SD. Significant differences (p < 0.05) by two-way
Anova followed by Bonferoni post hoc test. 47
RESULTADOS E DISCUSSÃO – ARTIGO 3
Disease prevalence
Figure 3. General model to understand the effects of Hg, Se and Se/Hg ratio in the prevalence of metabolic diseases. Healthy
individuals were considered as control. Metabolic Syndrome (MS); Systemic Arterial Hypertension (SAH); Type 2 Diabetes mellitus
(T2DM); Cardiovascular Disease (CVD). Data are presented as percentages. Significant differences (p < 0.05) by Kruskal-Wallis
analysis followed by chi-square test. 48
RESULTADOS E DISCUSSÃO – ARTIGO 3
A B
Figure 4. Mortality percentage among elderly riverine and the consumption of guarana. (A) Hg (0.011 µg/g); (B) Se (0.147
µg/g); (C) Se/Hg ratio. Data are presented as percentage. Significant differences (p < 0.05) by Kruskal-Wallis analysis
followed by chi-square test. 49
RESULTADOS E DISCUSSÃO – ARTIGO 3
Figure 5. Kaplan-Meier survival
curves for mortality in riparian
elderly by the influence of each
marker at their 50th percentile. (A)
Hg (0.011 µg.g-1), (B) Se (0.147
µg.g-1) and (C) Se/Hg (13.84 µg.g-
1).Dotted line: higher level, Full line:
A B
p = 0,020
C
50
RESULTADOS E DISCUSSÃO – ARTIGO 3
p = 0.004
Figure 6. Kaplan-Meier survival curves for mortality in
riparian elderly by the influence of different levels of Hg,
Se and Se/Hg ratio, all at 50th percentile, and with and
Control Guarana
without the combination of the effect of guarana. (A an B)
Hg (0.011 µg.g-1), (C and D) Se (0.147 µg.g-1) and (E
A B
and F) Se/Hg (13.84 µg.g-1). Control: no guarana intake;
Guarana: habitual intake (5 or more days/week). Dotted
line: higher level, Full line: lower level. Significant
p = 0.359
differences (p < 0.05) by Kaplan-Meier survival analysis.
Control Guarana
C D
p = 0.019
Control Guarana
51
E F
RESULTADOS E DISCUSSÃO – ARTIGO 3
p = 0.852 Figure 7. Kaplan-Meier survival curves for mortality in riparian
elderly by the influence of different levels of Se/Hg with and
without the combination of the effect of guarana. (A) 25th
percentile (12.25 µg.g-1), (B) 50th percentile (13.84 µg.g-1) and
Control Guarana (C) 75th percentile (17.11 µg.g-1) and combined with the
effect of guarana. Dotted line: higher level, Full line: lower
A level. Significant differences (p < 0.05) by Kaplan-Meier
B survival analysis.
p = 0.019
Control Guarana
C D
p =0.002
Control Guarana
E F 52
RESULTADOS E DISCUSSÃO – ARTIGO 3
55
CONCLUSÕES
56
CONCLUSÕES
57
REFERÊNCIAS
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Molecular Research, v. 12, n. 4, p. 5134–5144, 2013.
ALGARVE, T. D. et al. Parental and preimaginal exposure to methylmercury disrupts locomotor activity and circadian rhythm of adult Drosophila melanogaster. v. (Ahead of print),
p. 11, 2018.
ANTONINI, T. C. et al. Impact of functional determinants on 5.5-year mortality in Amazon riparian elderly. Revista Panamericana De Salud Publica = Pan American Journal
of Public Health, v. 40, n. 1, p. 9–15, ago. 2016.
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