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1.
JMIR Public Health Surveill ; 9: e44647, 2023 05 30.
Article de Anglais | MEDLINE | ID: mdl-37252771

RÉSUMÉ

BACKGROUND: Multimorbidity is characterized by the co-occurrence of 2 or more chronic diseases and has been a focus of the health care sector and health policy makers due to its severe adverse effects. OBJECTIVE: This paper aims to use the latest 2 decades of national health data in Brazil to analyze the effects of demographic factors and predict the impact of various risk factors on multimorbidity. METHODS: Data analysis methods include descriptive analysis, logistic regression, and nomogram prediction. The study makes use of a set of national cross-sectional data with a sample size of 877,032. The study used data from 1998, 2003, and 2008 from the Brazilian National Household Sample Survey, and from 2013 and 2019 from the Brazilian National Health Survey. We developed a logistic regression model to assess the influence of risk factors on multimorbidity and predict the influence of the key risk factors in the future, based on the prevalence of multimorbidity in Brazil. RESULTS: Overall, females were 1.7 times more likely to experience multimorbidity than males (odds ratio [OR] 1.72, 95% CI 1.69-1.74). The prevalence of multimorbidity among unemployed individuals was 1.5 times that of employed individuals (OR 1.51, 95% CI 1.49-1.53). Multimorbidity prevalence increased significantly with age. People over 60 years of age were about 20 times more likely to have multiple chronic diseases than those between 18 and 29 years of age (OR 19.6, 95% CI 19.15-20.07). The prevalence of multimorbidity in illiterate individuals was 1.2 times that in literate ones (OR 1.26, 95% CI 1.24-1.28). The subjective well-being of seniors without multimorbidity was 15 times that among people with multimorbidity (OR 15.29, 95% CI 14.97-15.63). Adults with multimorbidity were more than 1.5 times more likely to be hospitalized than those without (OR 1.53, 95% CI 1.50-1.56) and 1.9 times more likely need medical care (OR 1.94, 95% CI 1.91-1.97). These patterns were similar in all 5 cohort studies and remained stable for over 21 years. A nomogram model was used to predict multimorbidity prevalence under the influence of various risk factors. The prediction results were consistent with the effects of logistic regression; older age and poorer participant well-being had the strongest correlation with multimorbidity. CONCLUSIONS: Our study shows that multimorbidity prevalence varied little in the past 2 decades but varies widely across social groups. Identifying populations with higher rates of multimorbidity prevalence may improve policy making around multimorbidity prevention and management. The Brazilian government can create public health policies targeting these groups, and provide more medical treatment and health services to support and protect the multimorbidity population.


Sujet(s)
Multimorbidité , Adulte , Mâle , Femelle , Humains , Adulte d'âge moyen , Sujet âgé , Comorbidité , Brésil/épidémiologie , Études transversales , Maladie chronique
2.
JMIR Public Health Surveill ; 7(11): e29693, 2021 11 25.
Article de Anglais | MEDLINE | ID: mdl-34842558

RÉSUMÉ

BACKGROUND: Multimorbidity is the co-occurrence of two or more chronic diseases. OBJECTIVE: This study, based on self-reported medical diagnosis, aims to investigate the dynamic distribution of multimorbidity across sociodemographic levels and its impacts on health-related issues over 15 years in Brazil using national data. METHODS: Data were analyzed using descriptive statistics, hypothesis tests, and logistic regression. The study sample comprised 679,572 adults (18-59 years of age) and 115,699 elderly people (≥60 years of age) from the two latest cross-sectional, multiple-cohort, national-based studies: the National Sample Household Survey (PNAD) of 1998, 2003, and 2008, and the Brazilian National Health Survey (PNS) of 2013. RESULTS: Overall, the risk of multimorbidity in adults was 1.7 times higher in women (odds ratio [OR] 1.73, 95% CI 1.67-1.79) and 1.3 times higher among people without education (OR 1.34, 95% CI 1.28-1.41). Multiple chronic diseases considerably increased with age in Brazil, and people between 50 and 59 years old were about 12 times more likely to have multimorbidity than adults between 18 and 29 years of age (OR 11.89, 95% CI 11.27-12.55). Seniors with multimorbidity had more than twice the likelihood of receiving health assistance in community services or clinics (OR 2.16, 95% CI 2.02-2.31) and of being hospitalized (OR 2.37, 95% CI 2.21-2.56). The subjective well-being of adults with multimorbidity was often worse than people without multiple chronic diseases (OR=12.85, 95% CI: 12.07-13.68). These patterns were similar across all 4 cohorts analyzed and were relatively stable over 15 years. CONCLUSIONS: Our study shows little variation in the prevalence of the multimorbidity of chronic diseases in Brazil over time, but there are differences in the prevalence of multimorbidity across different social groups. It is hoped that the analysis of multimorbidity from the two latest Brazil national surveys will support policy making on epidemic prevention and management.


Sujet(s)
Multimorbidité , Maladies non transmissibles , Adulte , Sujet âgé , Brésil/épidémiologie , Maladie chronique , Études transversales , Femelle , Humains , Adulte d'âge moyen , Maladies non transmissibles/épidémiologie , Prévalence
3.
Biotechnol Bioeng ; 117(6): 1661-1672, 2020 06.
Article de Anglais | MEDLINE | ID: mdl-32068248

RÉSUMÉ

The available pneumococcal conjugate vaccines provide protection against only those serotypes that are included in the vaccine, which leads to a selective pressure and serotype replacement in the population. An alternative low-cost, safe and serotype-independent vaccine was developed based on a nonencapsulated pneumococcus strain. This study evaluates process intensification to improve biomass production and shows for the first time the use of perfusion-batch with cell recycling for bacterial vaccine production. Batch, fed-batch, and perfusion-batch were performed at 10 L scale using a complex animal component-free culture medium. Cells were harvested at the highest optical density, concentrated and washed using microfiltration or centrifugation to compare cell separation methods. Higher biomass was achieved using perfusion-batch, which removes lactate while retaining cells. The biomass produced in perfusion-batch would represent at least a fourfold greater number of doses per cultivation than in the previously described batch process. Each strategy yielded similar vaccines in terms of quality as evaluated by western blot and animal immunization assays, indicating that so far, perfusion-batch is the best strategy for the intensification of pneumococcal whole-cell vaccine production, as it can be integrated to the cell separation process keeping the same vaccine quality.


Sujet(s)
Techniques de culture cellulaire en batch/instrumentation , Vaccins antipneumococciques/immunologie , Streptococcus pneumoniae/immunologie , Animaux , Techniques de culture cellulaire en batch/méthodes , Biomasse , Bioréacteurs , Conception d'appareillage , Femelle , Humains , Immunisation , Souris de lignée C57BL , Infections à pneumocoques/immunologie , Infections à pneumocoques/prévention et contrôle , Vaccins antipneumococciques/usage thérapeutique , Pneumonie à pneumocoques/immunologie , Pneumonie à pneumocoques/prévention et contrôle , Streptococcus pneumoniae/cytologie
4.
Biotechnol Bioeng, p. 1-12, fev. 2020
Article de Anglais | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2983

RÉSUMÉ

The available pneumococcal conjugate vaccines provide protection against only those serotypes that are included in the vaccine, which leads to a selective pressure and serotype replacement in the population. An alternative low-cost, safe and serotype-independent vaccine was developed based on a nonencapsulated pneumococcus strain. This study evaluates process intensification to improve biomass production and shows for the first time the use of perfusion-batch with cell recycling for bacterial vaccine production. Batch, fed-batch, and perfusion-batch were performed at 10 L scale using a complex animal component-free culture medium. Cells were harvested at the highest optical density, concentrated and washed using microfiltration or centrifugation to compare cell separation methods. Higher biomass was achieved using perfusion-batch, which removes lactate while retaining cells. The biomass produced in perfusion-batch would represent at least a fourfold greater number of doses per cultivation than in the previously described batch process. Each strategy yielded similar vaccines in terms of quality as evaluated by western blot and animal immunization assays, indicating that so far, perfusion-batch is the best strategy for the intensification of pneumococcal whole-cell vaccine production, as it can be integrated to the cell separation process keeping the same vaccine quality.

5.
mBio, v. 9, n. 5, e01949-18, out. 2018
Article de Anglais | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2589

RÉSUMÉ

Staphylococcus aureus is a major cause of morbidity and mortality worldwide. S. aureus colonizes 20 to 80% of humans at any one time and causes a variety of illnesses. Strains that are resistant to common antibiotics further complicate management. S. aureus vaccine development has been unsuccessful so far, largely due to the incomplete understanding of the mechanisms of protection against this pathogen. Here, we studied the role of different aspects of adaptive immunity induced by an S. aureus vaccine in protection against S. aureus bacteremia, dermonecrosis, skin abscess, and gastrointestinal (GI) colonization. We show that, depending on the challenge model, the contributions of vaccine-induced S. aureus-specific antibody and Th1 and Th17 responses to protection are different: antibodies play a major role in reducing mortality during S. aureus bacteremia, whereas Th1 or Th17 responses are essential for prevention of S. aureus skin abscesses and the clearance of bacteria from the GI tract. Both antibody- and T-cell-mediated mechanisms contribute to prevention of S. aureus dermonecrosis. Engagement of all three immune pathways results in the most robust protection under each pathological condition. Therefore, our results suggest that eliciting multipronged humoral and cellular responses to S. aureus antigens may be critical to achieve effective and comprehensive immune defense against this pathogen. IMPORTANCE S. aureus is a leading cause of healthcare- and community-associated bacterial infections. S. aureus causes various illnesses, including bacteremia, meningitis, endocarditis, pneumonia, osteomyelitis, sepsis, and skin and soft tissue infections. S. aureus colonizes between 20 and 80% of humans; carriers are at increased risk for infection and transmission to others. The spread of multidrug-resistant strains limits antibiotic treatment options. Vaccine development against S. aureus has been unsuccessful to date, likely due to an inadequate understanding about the mechanisms of immune defense against this pathogen. The significance of our work is in illustrating the necessity of generating multipronged B-cell, Th1-, and Th17-mediated responses to S. aureus antigens in conferring enhanced and broad protection against S. aureus invasive infection, skin and soft tissue infection, and mucosal colonization. Our work thus, provides important insights for future vaccine development against this pathogen.

6.
An Bras Dermatol ; 92(5 Suppl 1): 92-94, 2017.
Article de Anglais | MEDLINE | ID: mdl-29267458

RÉSUMÉ

Hyperpigmented mycosis fungoides is an extremely rare subtype of mycosis fungoides. It presents as multiple pigmented macules and patches without poikilodermatous changes and characterized by a CD8+ phenotype on immunohistochemistry. This report describes a typical case of hyperpigmented mycosis fungoides in a 62-year-old woman, who presented with a 7-year history of multiple hyperpigmented macules and patches on the trunk and right leg with progression over this half a year. Histology and immunohistochemical staining of skin samples confirmed the diagnosis of mycosis fungoides. She received psoralen plus ultraviolet A (PUVA) therapy. After an 8-week treatment, the erythematous changes cleared without recurrence during a 6-month follow-up period. An intractable hyperpigmented patch should raise the clinical suspicion of mycosis fungoides with sequential skin biopsy.


Sujet(s)
Hyperpigmentation/anatomopathologie , Mycosis fongoïde/anatomopathologie , Tumeurs cutanées/anatomopathologie , Biopsie , Lymphocytes T CD8+/anatomopathologie , Humains , Hyperpigmentation/traitement médicamenteux , Immunohistochimie , Mâle , Adulte d'âge moyen , Mycosis fongoïde/traitement médicamenteux , Puvathérapie/méthodes , Tumeurs cutanées/traitement médicamenteux , Résultat thérapeutique
7.
Clin Vaccine Immunol ; 24(10)2017 Oct.
Article de Anglais | MEDLINE | ID: mdl-28768668

RÉSUMÉ

Pneumococcal diseases remain a substantial cause of mortality in young children in developing countries. The development of potentially serotype-transcending vaccines has been extensively studied; ideally, such a vaccine should include antigens that are able to induce protection against colonization (likely mediated by interleukin-17A [IL-17A]) and invasive disease (likely mediated by antibody). The use of strong adjuvants or alternative delivery systems that are able to improve the immunological response of recombinant proteins has been proposed but poses potential safety and practical concerns in children. We have previously constructed a recombinant Mycobacterium bovis BCG strain expressing a pneumococcal surface protein A (PspA)-PdT fusion protein (rBCG PspA-PdT) that was able to induce an effective immune response and protection against sepsis in a prime-boost strategy. Here, we constructed two new rBCG strains expressing the pneumococcal proteins SP 0148 and SP 2108, which confer IL-17A-dependent protection against pneumococcal colonization in mouse models. Immunization of mice with rBCG 0148 or rBCG 2108 in a prime-boost strategy induced IL-17A and gamma interferon (IFN-γ) production. The combination of these rBCG strains with rBCG PspA-PdT (rBCG Mix), followed by a booster dose of the combined recombinant proteins (rMix) induced an IL-17A response against SP 0148 and SP 2108 and a humoral response characterized by increased levels of IgG2c against PspA and functional antibodies against pneumolysin. Furthermore, immunization with the rBCG Mix prime/rMix booster (rBCG Mix/rMix) provides protection against pneumococcal colonization and sepsis. These results suggest the use of combined rBCG strains as a potentially serotype-transcending pneumococcal vaccine in a prime-boost strategy, which could provide protection against pneumococcal colonization and sepsis.


Sujet(s)
Immunité cellulaire , Immunité humorale , Mycobacterium bovis/génétique , Infections à pneumocoques/prévention et contrôle , Vaccins antipneumococciques/immunologie , Sepsie/prévention et contrôle , Streptococcus pneumoniae/immunologie , Animaux , Anticorps antibactériens/sang , Antigènes bactériens/génétique , Antigènes bactériens/immunologie , Vaccin BCG/administration et posologie , Vaccin BCG/génétique , Vaccin BCG/immunologie , Modèles animaux de maladie humaine , Femelle , Immunisation , Rappel de vaccin , Immunoglobuline G/sang , Immunoglobuline G/immunologie , Interféron gamma/immunologie , Interleukine-17/immunologie , Souris , Mycobacterium bovis/immunologie , Infections à pneumocoques/immunologie , Vaccins antipneumococciques/administration et posologie , Sepsie/immunologie , Streptococcus pneumoniae/génétique , Streptococcus pneumoniae/physiologie , Vaccins synthétiques/immunologie
8.
Vaccine ; 35(13): 1683-1691, 2017 03 23.
Article de Anglais | MEDLINE | ID: mdl-28242071

RÉSUMÉ

Pneumococcal proteins have been evaluated as genetically-conserved potential vaccine candidates. We have previously demonstrated that a fragment of PspA in fusion with PdT (rPspA-PdT) induced protective immune responses in mice. However, purified proteins have shown poor immunogenicity and often require the combination with strong adjuvants and booster doses. Here, we investigated the use of a Bacillus Calmette-Guérin (BCG) strain, a well-established prophylactic vaccine for tuberculosis with known adjuvant properties, for delivery of the PspA-PdT fusion protein. Immunization of mice in a prime-boost strategy, using rPspA-PdT as a boost, demonstrated that rBCG PspA-PdT/rPspA-PdT was able to induce an antibody response against both proteins, promoting an IgG1 to IgG2 antibody isotype shift. Sera from rBCG PspA-PdT/rPspA-PdT immunized mice showed antibodies able to bind to the pneumococcal surface and promoted higher complement deposition when compared with WT-BCG/rPspA-PdT or a single dose of rPspA-PdT. In addition, these antisera inhibited the cytolytic activity of Ply. Production of interleukin-6 (IL-6), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) was increased in splenocytes culture. Furthermore, a higher expression of CD69 early activation molecule was observed on splenic CD4+ T cells from mice immunized with rBCG PspA-PdT before and after the protein booster dose. Finally, immunization with rBCG PspA-PdT/rPspA-PdT protected mice against pneumococcal lethal challenge. These results support the further investigation of recombinant BCG strains to express pneumococcal proteins, which could be administered in early stages of life and lead to protective pneumococcal immunity in infants and children.


Sujet(s)
Protéines bactériennes/immunologie , Vecteurs de médicaments , Calendrier vaccinal , Mycobacterium bovis/génétique , Infections à pneumocoques/prévention et contrôle , Vaccins antipneumococciques/immunologie , Protéines de fusion recombinantes/immunologie , Animaux , Anticorps antibactériens/sang , Antigènes CD/analyse , Antigènes de différenciation des lymphocytes T/analyse , Protéines bactériennes/génétique , Lymphocytes T CD4+/composition chimique , Lymphocytes T CD4+/immunologie , Cytokines/métabolisme , Modèles animaux de maladie humaine , Femelle , Immunoglobuline G/sang , Lectines de type C/analyse , Souris de lignée C57BL , Vaccins antipneumococciques/administration et posologie , Vaccins antipneumococciques/génétique , Protéines de fusion recombinantes/génétique , Analyse de survie , Résultat thérapeutique , Vaccins synthétiques/administration et posologie , Vaccins synthétiques/génétique , Vaccins synthétiques/immunologie
9.
Vaccine ; 35(9): 1306-1315, 2017 03 01.
Article de Anglais | MEDLINE | ID: mdl-28161422

RÉSUMÉ

The pneumococcal whole cell vaccine (PWCV) has been investigated as an alternative to polysaccharide-based vaccines currently in use. It is a non-encapsulated killed vaccine preparation that induces non-capsular antibodies protecting mice against invasive pneumococcal disease (IPD) and reducing nasopharyngeal (NP) carriage via IL-17A activation of mouse phagocytes. Here, we show that PWCV induces antibody and IL-17A production to protect mice against challenge in a fatal aspiration-sepsis model after only one dose. We observed protection even with a boiled preparation, attesting to the stability and robustness of the vaccine. PWCV antibodies were shown to bind to different encapsulated strains, but complement deposition on the pneumococcal surface was observed only on serotype 3 strains; using flow cytometer methodology, variations in PWCV quality, as in the boiled vaccine, were detected. Moreover, anti-PWCV induces phagocytosis of different pneumococcal serotypes by murine peritoneal cells in the presence of complement or IL-17A. These findings suggest that complement and IL-17A may participate in the process of phagocytosis induced by PWCV antibodies. IL-17A can stimulate phagocytic cells to kill pneumococcus and this is enhanced in the presence of PWCV antibodies bound to the bacterial cell surface. Our results provide further support for the PWCV as a broad-range vaccine against all existing serotypes, potentially providing protection for humans against NP colonization and IPD. Additionally, we suggest complement deposition assay as a tool to detect subtle differences between PWCV lots.


Sujet(s)
Complément C3/immunologie , Interleukine-17/immunologie , Infections à pneumocoques/immunologie , Infections à pneumocoques/prévention et contrôle , Vaccins antipneumococciques/immunologie , Streptococcus pneumoniae/immunologie , Animaux , Sites de fixation des anticorps , Cytométrie en flux , Souris , Partie nasale du pharynx/microbiologie , Opsonines/immunologie , Phagocytose , Vaccins antipneumococciques/administration et posologie , Sepsie/immunologie , Sepsie/microbiologie , Sepsie/prévention et contrôle , Sérogroupe , Vaccins inactivés/administration et posologie , Vaccins inactivés/immunologie
10.
An. bras. dermatol ; An. bras. dermatol;92(5,supl.1): 92-94, 2017. graf
Article de Anglais | LILACS | ID: biblio-887103

RÉSUMÉ

Abstract Hyperpigmented mycosis fungoides is an extremely rare subtype of mycosis fungoides. It presents as multiple pigmented macules and patches without poikilodermatous changes and characterized by a CD8+ phenotype on immunohistochemistry. This report describes a typical case of hyperpigmented mycosis fungoides in a 62-year-old woman, who presented with a 7-year history of multiple hyperpigmented macules and patches on the trunk and right leg with progression over this half a year. Histology and immunohistochemical staining of skin samples confirmed the diagnosis of mycosis fungoides. She received psoralen plus ultraviolet A (PUVA) therapy. After an 8-week treatment, the erythematous changes cleared without recurrence during a 6-month follow-up period. An intractable hyperpigmented patch should raise the clinical suspicion of mycosis fungoides with sequential skin biopsy.


Sujet(s)
Humains , Mâle , Adulte d'âge moyen , Tumeurs cutanées/anatomopathologie , Mycosis fongoïde/anatomopathologie , Hyperpigmentation/anatomopathologie , Puvathérapie/méthodes , Tumeurs cutanées/traitement médicamenteux , Biopsie , Immunohistochimie , Mycosis fongoïde/traitement médicamenteux , Résultat thérapeutique , Hyperpigmentation/traitement médicamenteux , Lymphocytes T CD8+/anatomopathologie
11.
Brain Behav Evol ; 88(3-4): 204-212, 2016.
Article de Anglais | MEDLINE | ID: mdl-27820927

RÉSUMÉ

Losses of cone opsin genes are noted in animals that are nocturnal or rely on senses other than vision. We investigated the cone opsin repertoire of night-active South American weakly electric fish. We obtained opsin gene sequences from genomic DNA of 3 gymnotiforms (Eigenmannia virescens, Sternopygus macrurus, Apteronotus albifrons) and the assembled genome of the electric eel (Electrophorus electricus). We identified genes for long-wavelength-sensitive (LWS) and medium-wavelength-sensitive cone opsins (RH2) and rod opsins (RH1). Neither of the 2 short-wavelength-sensitive cone opsin genes were found and are presumed lost. The fact that Electrophorus has a complete repertoire of extraretinal opsin genes and conservation of synteny with the zebrafish (Danio rerio) for genes flanking the 2 short-wavelength-sensitive opsin genes supports the supposition of gene loss. With microspectrophotometry and electroretinograms we observed absorption spectra consistent with RH1 and LWS but not RH2 opsins in the retinal photoreceptors of E. virescens. This profile of opsin genes and their retinal expression is identical to the gymnotiform's sister group, the catfish, which are also nocturnally active and bear ampullary electroreceptors, suggesting that this pattern likely occurred in the common ancestor of gymnotiforms and catfish. Finally, we noted an unusual N-terminal motif lacking a conserved glycosylation consensus site in the RH2 opsin of gymnotiforms, a catfish and a characin (Astyanax mexicanus). Mutations at this site influence rhodopsin trafficking in mammalian photoreceptors and cause retinitis pigmentosa. We speculate that this unusual N terminus may be related to the absence of the RH2 opsin in the cones of gymnotiforms and catfish.


Sujet(s)
Opsines des cônes/génétique , Expression des gènes/physiologie , Gymnotiformes/physiologie , Cellules photoréceptrices en cône de la rétine/physiologie , Animaux , Electrophorus/génétique , Electrophorus/physiologie , Électrorétinographie , Expression des gènes/génétique , Génome , Gymnotiformes/génétique , Microspectrophotométrie , Amérique du Sud
12.
Environ Int ; 95: 54-60, 2016 Oct.
Article de Anglais | MEDLINE | ID: mdl-27502898

RÉSUMÉ

BACKGROUND: Boron is a metalloid found at highly varying concentrations in soil and water. Experimental data indicate that boron is a developmental toxicant, but the few human toxicity data available concern mostly male reproduction. OBJECTIVES: To evaluate potential effects of boron exposure through drinking water on pregnancy outcomes. METHODS: In a mother-child cohort in northern Argentina (n=194), 1-3 samples of serum, whole blood and urine were collected per woman during pregnancy and analyzed for boron and other elements to which exposure occurred, using inductively coupled plasma mass spectrometry. Infant weight, length and head circumference were measured at birth. RESULTS: Drinking water boron ranged 377-10,929µg/L. The serum boron concentrations during pregnancy ranged 0.73-605µg/L (median 133µg/L) and correlated strongly with whole-blood and urinary boron, and, to a lesser extent, with water boron. In multivariable-adjusted linear spline regression analysis (non-linear association), we found that serum boron concentrations above 80µg/L were inversely associated with birth length (B-0.69cm, 95% CI -1.4; -0.024, p=0.043, per 100µg/L increase in serum boron). The impact of boron appeared stronger when we restricted the exposure to the third trimester, when the serum boron concentrations were the highest (0.73-447µg/L). An increase in serum boron of 100µg/L in the third trimester corresponded to 0.9cm shorter and 120g lighter newborns (p=0.001 and 0.021, respectively). CONCLUSIONS: Considering that elevated boron concentrations in drinking water are common in many areas of the world, although more screening is warranted, our novel findings warrant additional research on early-life exposure in other populations.


Sujet(s)
Poids de naissance , Bore/toxicité , Eau de boisson/composition chimique , Grossesse/sang , Adolescent , Adulte , Argentine , Bore/sang , Études de cohortes , Femelle , Humains , Nouveau-né , Mâle , Issue de la grossesse , Jeune adulte
13.
Environ Res ; 147: 1-7, 2016 May.
Article de Anglais | MEDLINE | ID: mdl-26828622

RÉSUMÉ

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5-1660µg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D3, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25µg/L (range 1.9-145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D3 (-6.1nmol/L [95%CI -9.5; -2.6] for a 25µg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D3. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25µg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water.


Sujet(s)
Calcium/sang , Calcium/urine , Eau de boisson/analyse , Exposition environnementale , Homéostasie , Lithium/métabolisme , Polluants chimiques de l'eau/métabolisme , Adolescent , Adulte , Argentine , Marqueurs biologiques/sang , Marqueurs biologiques/urine , Femelle , Humains , Lithium/analyse , Lithium/sang , Lithium/urine , Études longitudinales , Grossesse , Polluants chimiques de l'eau/analyse , Polluants chimiques de l'eau/sang , Polluants chimiques de l'eau/urine , Jeune adulte
14.
Environ Res ; 147: 16-23, 2016 May.
Article de Anglais | MEDLINE | ID: mdl-26828624

RÉSUMÉ

Arsenic exposure in children is a public health concern but is understudied in relation to the predictors, and effects of low-level exposure. We examined the extent and dietary predictors of exposure to inorganic arsenic in 5-8 year old children from Montevideo, Uruguay. Children were recruited at school; 357 were enrolled, 328 collected morning urine samples, and 317 had two 24-h dietary recalls. Urinary arsenic metabolites, i.e. inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were measured using high-performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICP-MS), and the sum concentration (U-As) used for exposure assessment. Proportions of arsenic metabolites (%iAs, %MMA and %DMA) in urine were modelled in OLS regressions as functions of food groups, dietary patterns, nutrient intake, and nutritional status. Exposure to arsenic was low (median U-As: 9.9µg/L) and household water (water As: median 0.45µg/L) was not a major contributor to exposure. Children with higher consumption of rice had higher U-As but lower %iAs, %MMA, and higher %DMA. Children with higher meat consumption had lower %iAs and higher %DMA. Higher scores on "nutrient dense" dietary pattern were related to lower %iAs and %MMA, and higher %DMA. Higher intake of dietary folate was associated with lower %MMA and higher %DMA. Overweight children had lower %MMA and higher %DMA than normal-weight children. In summary, rice was an important predictor of exposure to inorganic arsenic and DMA. Higher meat and folate consumption, diet rich in green leafy and red-orange vegetables and eggs, and higher BMI contributed to higher arsenic methylation capacity.


Sujet(s)
Arsenic/analyse , Arsenic/urine , Composés de l'arsenic/urine , Régime alimentaire , Eau de boisson/analyse , Exposition environnementale , État nutritionnel , Enfant , Enfant d'âge préscolaire , Chromatographie en phase liquide à haute performance , Surveillance de l'environnement , Femelle , Humains , Mâle , Spectrométrie de masse , Uruguay
15.
Vaccine ; 28(47): 7468-7475, 2010.
Article de Anglais | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP, SESSP-IBACERVO | ID: biblio-1068348

RÉSUMÉ

Mucosal immunization with a killed whole-cell pneumococcal vaccine, given with enterotoxin-related adjuvants, has been shown to confer multi-serotype protection against colonization of the nasopharynx and middle ear in mice. However, because novel mucosal immunization strategies may be difficult to implement, here we evaluated subcutaneous injection. Strain RM200 was engineered to be capsule-negative, autolysin-negative, and to express a non-toxic mutant pneumolysoid. Liter-scale and 60-l Good Manufacturing Practice (GMP) cultures were grown in bovine-free soy-based medium, killed with chloroform or beta-propiolactone, and injected into C57Bl/6 mice without or with aluminum adjuvant. The adjuvant Al(OH)3 strongly increased responses, particularly if pre-treated with phosphate. Protection was found in several tested model infections: nasal colonization with a serotype 6B strain and fatal aspiration-sepsis with strains of serotype 3 and 5. Protection against colonization was mechanistically dependent on the presence of CD4+ T cells at the time of challenge; in contrast, in the type 3 aspiration-sepsis model, CD4+ T cells were not required for protection at the time of challenge, suggesting that antibody alone was sufficient to protect against death in this model. Rabbits receiving sequential intramuscular injections in a pilot toxicity study displayed local reactogenicity at injection sites but no clinical signs. The rabbit antiserum thus produced was active in an in vitro phagocytic killing assay and passively protected mice in the type 3 aspiration-sepsis model. Approval is being sought for human trials of this vaccine.


Sujet(s)
Humains , Animaux , Rats , Streptococcus pneumoniae/immunologie , Vaccins
16.
AIDS ; 23(6): 731-7, 2009 Mar 27.
Article de Anglais | MEDLINE | ID: mdl-19279446

RÉSUMÉ

OBJECTIVE: The influence of viral subtype on the natural history of HIV is unclear and confounded by socioeconomic and host factors that vary between groups harboring different clades. We compared Canadians (clade B), with recent immigrants from Haiti (clade B) and sub-Saharan Africa (clades non-B) to determine whether there were differences in disease progression attributable to viral subtype. METHODS: We conducted a retrospective cohort study in a universal healthcare setting between 1996 and 2007. The rate of CD4+ T-lymphocyte decline prior to initiation of antiretroviral therapy was determined in all participants with at least two CD4+ T-lymphocyte measures using mixed linear regression models. Time to first AIDS-defining illness was compared using adjusted Cox proportional hazards models. RESULTS: Two hundred and eighty-nine Canadians, 44 Haitians, and 123 Africans were studied for a median of 260 days (2 days-11 years). Africans and Haitians were demographically and clinically similar. However, the adjusted slope of square root CD4+ T-lymphocyte decline was significantly lower in Africans [-0.04/year; 95% confidence interval (CI) = -0.08 to -0.003] compared with Canadians (-0.07/year; 95% CI = -0.11 to -0.03; P = 0.02), and Haitians (-0.10/year; 95% CI = -0.12 to -0.07; P = 0.001). Africans were also less likely to develop AIDS. CONCLUSION: Despite having similar demographic, socioeconomic, and nutritional status to Haitians, Africans infected with non-B clade HIV had slower rates of disease progression compared with both Haitians and Canadians, with both groups being infected by the clade B virus. Our findings suggest that viral subtype may be an important predictor of HIV natural history in a developed medical setting.


Sujet(s)
Infections à VIH/virologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/classification , Adolescent , Adulte , Afrique subsaharienne/ethnologie , 38410/statistiques et données numériques , Numération des lymphocytes CD4 , Lymphocytes T CD4+/immunologie , 28601 , Évolution de la maladie , Femelle , Infections à VIH/ethnologie , Infections à VIH/immunologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/génétique , Haïti/ethnologie , Humains , Mâle , Adulte d'âge moyen , Pronostic , Québec/épidémiologie , Jeune adulte
17.
Anal Bioanal Chem ; 382(7): 1616-9, 2005 Aug.
Article de Anglais | MEDLINE | ID: mdl-15999270

RÉSUMÉ

A simple and sensitive method is described for determination of jasmonic acid (JA) in plant tissues. The method is based on derivatization of JA with 5-bromomethylfluorescein (5-BMF) and separation and quantification of the resulting 5-BMF-JA derivative by capillary electrophoresis coupled to laser-induced fluorescence detection (CE-LIF). The derivatization conditions were studied in detail. Our results indicated that 5-BMF-labeled JA could be well separated from other plant hormones present in the sample by use of 20 mmol L(-1) borate buffer (pH 8.5). The response to JA was a linear function of concentration in the range 1 to 100 micromol L(-1), with a correlation of 0.9986. Our preliminary work showed that the proposed method had fairly good selectivity and sensitivity. Only small amounts of plant sample are needed to complete the analysis. This described method enables the analysis of JA in crude extracts without extra purification and enrichment procedures.


Sujet(s)
Cyclopentanes/isolement et purification , Hevea/composition chimique , Lasers , Électrophorèse capillaire , Oxylipines , Écorce/composition chimique , Extraits de plantes/isolement et purification , Reproductibilité des résultats , Sensibilité et spécificité , Spectrométrie de fluorescence
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