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1.
Nature ; 625(7996): 760-767, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38092039

RESUMO

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1-4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with ß-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.


Assuntos
Fator 15 de Diferenciação de Crescimento , Hiperêmese Gravídica , Náusea , Vômito , Animais , Feminino , Humanos , Camundongos , Gravidez , Talassemia beta/sangue , Talassemia beta/metabolismo , Feto/metabolismo , Fator 15 de Diferenciação de Crescimento/sangue , Fator 15 de Diferenciação de Crescimento/metabolismo , Hormônios/sangue , Hormônios/metabolismo , Hiperêmese Gravídica/complicações , Hiperêmese Gravídica/metabolismo , Hiperêmese Gravídica/prevenção & controle , Hiperêmese Gravídica/terapia , Náusea/sangue , Náusea/complicações , Náusea/metabolismo , Placenta/metabolismo , Vômito/sangue , Vômito/complicações , Vômito/metabolismo
2.
J Intellect Disabil Res ; 68(4): 358-368, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38183401

RESUMO

BACKGROUND: Children and adolescents with Down syndrome (DS) may experience impairments in sensory and motor skills that can be interrelated. The purposes of this study were (i) to compare the sensory processing patterns and gross motor function between children and adolescents with DS and with typical development (TD) and (ii) to explore associations between these areas in both DS and TD groups. METHOD: This cross-sectional study involved a sample size of 25 participants with DS (mean age 10.24 ± 2.04 years) and 25 participants with TD (mean age 10.04 ± 2.82 years). The sensory processing patterns were assessed using the Sensory Profile Second Version questionnaire, and the gross motor function was measured with the Gross Motor Function Measure (GMFM-88) dimensions (D) standing, and (E) walking, running, and jumping. Differences between groups were tested using the Mann-Whitney test, and the relationship between the variables was examined using Spearman's correlation tests, with a significance level set at 5%. RESULTS: Children with DS showed greater difficulties with sensory processing than TD children in Seeker (P < 0.001), Avoider (P < 0.001), Sensitivity (P < 0.001), Registration (P < 0.001), Auditory (P < 0.001), Touch (P = 0.001), Movements (P = 0.001), Oral (P = 0.028), Conduct (P = 0.005), Socioemotional (P < 0.001), and Attentional (P < 0.001) domains. Additionally, children with DS presented lower gross motor function than TD in GMFM-88, standing (P < 0.001) and walking, running, and jumping (P < 0.001). Correlations were found between greater difficulties with sensory processing in Touch and lower gross motor function in walking, running, and jumping for the DS group. CONCLUSION: Our results suggest there are more difficulties in sensory processing patterns and gross motor function in children with DS than in TD. Also, there is a single association between more difficulties in sensory processing and less well-developed motor function in the DS group. Therefore, a comprehensive assessment of all these aspects should be performed in children and adolescents with DS, along with the provision of relevant interventions addressing specific needs.


Assuntos
Síndrome de Down , Percepção do Tato , Criança , Humanos , Adolescente , Estudos Transversais , Desenvolvimento Infantil , Destreza Motora
3.
Public Health ; 201: 78-88, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34798327

RESUMO

OBJECTIVE: To analyze the literature to determine whether autohemotherapy has any effect either clinically or on the immune system on viral diseases on the last ten years. STUDY DESIGN: Systematic review. METHODS: Searches from the year 2010, with at least 5 patients were conducted in PubMed/MEDLINE, Embase, Scopus, Cochrane, LILACS, SciELO, and Web of Science databases. Hand searches were performed in systematic reviews and literature reviews related to autohemotherapy. Unpublished manuscripts were hand-searched in specialized journals. RESULTS: Eight articles were included. Hepatitis B virus, hepatitis C virus, and Coronavirus were evaluated. Autohemotherapy had good results in hepatitis C, hepatitis B, and Coronavirus. CONCLUSION: Autohemotherapy is a safe practice that improves symptoms in the treatment of hepatitis B virus, hepatitis C virus, and Coronavirus. It is necessary to perform more prospective comparative studies with homogeneous protocols.


Assuntos
Infecções por Coronavirus , Viroses , Humanos , Estudos Prospectivos , Viroses/terapia
4.
Crit Rev Food Sci Nutr ; 60(4): 660-669, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30596263

RESUMO

Vitamin D deficiency is considered a global public health problem with high prevalence in children and adolescents. The majority of the studies in the literature have identified a relationship between vitamin D insufficiency/deficiency and obesity, as well as other traditional cardiometabolic risk factors in children and adolescents. Scarce studies address vitamin D status with oxidative stress and inflammation in the young population. The aim of this systematic review was to evaluate the evidence of the association of vitamin D status with oxidative stress and inflammation in children and adolescents. This is a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guideline on reporting systematic reviews. Eight studies were selected for this review. All included studies evaluated inflammatory biomarkers and two out of eight evaluated biomarkers of oxidative stress. The majority of the studies (five out of eight) found association of vitamin D status with biomarkers of oxidative stress and inflammation such as C-reactive protein (CRP), interleukin-6 (IL-6), cathepsin S, vascular cell adhesion molecule-1 (VCAM-1), malondialdehyde (MDA), myeloperoxidase, 3-nitrotyrosine, and superoxide dismutase (SOD). Vitamin D status is associated with oxidative stress and inflammation in the majority of the studies with children and adolescents. Thus, the assessment of vitamin D status is important because it is associated with nontraditional cardiometabolic markers in the pediatric population (review registration: PROSPERO CRD42018109307).


Assuntos
Inflamação/sangue , Inflamação/metabolismo , Estresse Oxidativo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/metabolismo , Vitamina D/análise , Vitamina D/metabolismo , Adolescente , Biomarcadores/sangue , Biomarcadores/metabolismo , Criança , Humanos , Vitaminas/sangue , Vitaminas/metabolismo
5.
J Intellect Disabil Res ; 63(6): 576-586, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30687997

RESUMO

BACKGROUND: Cognitive and postural tasks require common cognitive mechanisms, resulting in conflicts when both tasks are simultaneously performed. The presence of neuromotor dysfunctions, such as Down syndrome, may impair coordination processes required to perform dual-tasks. The objective of this study was to investigate the dual-task effects on postural sway during sit-to-stand movements in typical children and children with Down syndrome in a cross-sectional study. METHODS: Twenty six typical children (10.2 ± 2.4 years) and 21 with Down syndrome (10.3 ± 2.3 years) performed sit-to-stand in the following conditions: (1) simple task; (2) dual-task bimanual activity (DT-Bim): sit-to-stand while carrying a tray using both hands; (3) dual-task unimanual dominant activity (DT-Uni-Dom): sit-to-stand while holding a plastic cup simulating water using the dominant hand; (4) dual-task unimanual non-dominant activity (DT-Uni-Nondom): sit-to-stand movement while holding a plastic cup simulating water. For data analysis, sit-to-stand was divided into three phases: preparation (phase 1), rising (phase 2), and stabilisation (phase 3). The following variables were calculated for each phase: anterior-posterior and medial-lateral amplitude of centre-of-pressure displacement, anterior-posterior and medial-lateral velocity of centre-of-pressure sway and area of centre-of-pressure sway. RESULTS: Children with Down syndrome showed greater sway than typical children in all sit-to-stand phases. Typical children showed greater anterior-posterior amplitude in phase 2 of sit-to-stand during DT-Uni Nondom compared with DT-Uni Dom. Children with Down syndrome during simple task condition showed greater and faster values sway in phases 2 and 3 of sit-to-stand movement than in DT-Bim activity, DT-Uni Dom activity and DT-Uni Nondom activity. During the condition of DT-Bim activity, these children showed lower anterior-posterior velocity of sway in phase 2 than during DT-Uni Dom activity. CONCLUSIONS: Children with Down syndrome showed greater postural sway during sit-to-stand than typical children. The addition of a concurrent motor task to sit-to-stand impacted postural sway in different intensities and in different ways across groups. Dual-tasks increased body sway in typical children in the DT-Uni Nondom condition compared with dominant one. In children with Down syndrome, dual-tasks decreased body sway, apparently resulting in a postural strategy of stiffness.


Assuntos
Síndrome de Down/fisiopatologia , Função Executiva/fisiologia , Atividade Motora/fisiologia , Equilíbrio Postural/fisiologia , Desempenho Psicomotor/fisiologia , Postura Sentada , Posição Ortostática , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino
7.
Med Vet Entomol ; 32(1): 111-114, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28799248

RESUMO

A polymerase chain reaction-based method was used to screen sandflies for infection with Wolbachia (Rickettsiales: Rickettsiaceae), an intracellular bacterial endosymbiont found in many arthropods and filarial hosts. Positive results were obtained in five of 200 field-collected sandflies and were confirmed by sequencing. All sandflies were Lutzomyia longipalpis (Diptera: Psychodidae) captured in a region endemic for visceral leishmaniasis in Brazil. This is the first study to identify Wolbachia infection in this Lutzomyia species, which is the main vector of leishmaniasis in the study area. The low infection rate found in this study (2.5%), together with the lack of detection of Wolbachia in previous studies and the diversity found in the sequences analysed, suggests horizontal transmission to these sandflies.


Assuntos
Insetos Vetores/microbiologia , Psychodidae/microbiologia , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Wolbachia/isolamento & purificação , Animais , Brasil , Controle de Doenças Transmissíveis/métodos , Feminino , Haplótipos , Leishmania infantum/fisiologia , Leishmaniose Visceral/transmissão , Masculino , Reação em Cadeia da Polimerase , Análise de Sequência de RNA
8.
Lupus ; 26(1): 10-16, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27365371

RESUMO

OBJECTIVES: To analyze the association of adipokines and tumor necrosis factor α (TNFα) and its receptors with characteristics of systemic lupus erythematosus (SLE) and to investigate the correlation between adipokines and the TNF system. METHODS: One hundred and thirty-six SLE women, aged ≥18 years old, were assessed. TNFα, soluble TNFα receptors 1 (sTNFR1) and 2 (sTNFR2) and adipokines were analyzed by ELISA kits. RESULTS: The median (IQR) of age was 41.5 (33.0-49.7) years old and of disease duration 11.3 (7.8-15.8) years. The median (IQR) of disease activity was 0 (0-4) and of damage index was 2 (1-3). Higher levels of sTNFR1 and sTNFR2 were associated with nephritis (p < 0.001 for both), and sTNFR1 (p = 0.025) and TNFα (p = 0.014) were positively associated with arthritis. Higher sTNFR1 levels were found in participants that were not using antimalarial drugs (p = 0.04). Independent correlation was found between sTNFR1 (ß = 0.253; p = 0.003) and sTNFR2 (ß = 0.297; p < 0.001) levels and disease activity and damage index (sTNFR1: ß = 0.367; p < 0.001; sTNFR2: ß = 0.335; p < 0.001). Higher adiponectin levels were independently associated with nephritis (p = 0.009) and antimalarial drugs use (p = 0.015). There was a positive correlation between leptin and sTNFR2 levels (p = 0.002) and between resistin levels and sTNFR1 (p < 0.001) and sTNFR2 (p < 0.001). CONCLUSION: The correlation between adipokines and TNF system allows a better understanding of the role of adipokines in the inflammatory response in SLE patients.


Assuntos
Adipocinas/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Nefrite Lúpica/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Antimaláricos/administração & dosagem , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Leptina/metabolismo , Pessoa de Meia-Idade , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Resistina/metabolismo , Índice de Gravidade de Doença
9.
J Intellect Disabil Res ; 61(8): 755-765, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28585394

RESUMO

BACKGROUND: People with Down syndrome (DS) usually display reduced physical fitness (aerobic capacity, muscle strength and abnormal body composition), motor proficiency impairments (balance and postural control) and physical functional limitations. Exergames can be an appealing alternative to enhance exercise engagement and compliance, whilst improving physical fitness and motor function. This study aims to analyse the effects of a Wii-based exercise program on physical fitness, functional mobility and motor proficiency of adults with DS. METHODS: Twenty-seven adults with DS were randomly allocated to an experimental group (Wii; n = 14) or control group (n = 13). Participants in the experimental group completed a 2-month Wii-based exercise program, with three 1-h sessions per week that included training games for aerobic endurance, balance and isometric strength. Participants completed assessments regarding anthropometric measures, physical fitness, functional mobility and motor proficiency. RESULTS: Mixed ANOVA analysis showed a significant group by time interaction for aerobic endurance, explosive leg power and flexibility. Independent samples t-test for change scores indicated significant between-group differences favouring the experimental group regarding speed of limb movement, trunk strength and functional mobility, as well as a trend towards significance on body weight. Mann-Whitney's U test for change scores demonstrated between-group differences favouring the experimental group for visceral fat as well as running speed and agility. Large within-group effect sizes were observed for explosive leg power (d = 1.691), body weight (d = 1.281), functional mobility (d = 1.218), aerobic endurance (d = 1.020), speed of limb movement (d = 0.867) and flexibility (d = 0.818) in the experimental group. CONCLUSIONS: Our findings suggest that Wii-based exercise can be an effective tool to improve physical fitness, functional mobility and motor proficiency of adults with DS, including crucial measures such as aerobic capacity and lower limb strength. Exergames using Wii Fit or other equipment can be appealing alternatives for adults with DS to engage in regular physical activity, preventing sedentary behaviour and decreasing the risk to develop cardiovascular diseases.


Assuntos
Síndrome de Down/reabilitação , Terapia por Exercício/métodos , Avaliação de Resultados em Cuidados de Saúde , Terapia Assistida por Computador/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Jogos de Vídeo
10.
Scand J Med Sci Sports ; 26(11): 1360-1372, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27152850

RESUMO

Experimental studies have reported that aerobic exercise after asthma induction reduces lung inflammation and remodeling. Nevertheless, no experimental study has analyzed whether regular/moderate aerobic training before the induction of allergic asthma may prevent these inflammatory and remodeling processes. For this purpose, BALB/c mice (n = 96) were assigned into non-trained and trained groups. Trained animals ran on a motorized treadmill at moderate intensity, 30 min/day, 3 times/week, for 8 weeks, and were further randomized into subgroups to undergo ovalbumin sensitization and challenge or receive saline using the same protocol. Aerobic training continued until the last challenge. Twenty-four hours after challenge, compared to non-trained animals, trained mice exhibited: (a) increased systolic output and left ventricular mass on echocardiography; (b) improved lung mechanics; (c) decreased smooth muscle actin expression and collagen fiber content in airways and lung parenchyma; (d) decreased transforming growth factor (TGF)-ß levels in bronchoalveolar lavage fluid (BALF) and blood; (e) increased interferon (IFN)-γ in BALF and interleukin (IL)-10 in blood; and (f) decreased IL-4 and IL-13 in BALF. In conclusion, regular/moderate aerobic training prior to allergic asthma induction reduced inflammation and remodeling, perhaps through increased IL-10 and IFN-γ in tandem with decreased Th2 cytokines.


Assuntos
Remodelação das Vias Aéreas , Asma/imunologia , Citocinas/imunologia , Pulmão/imunologia , Condicionamento Físico Animal , Animais , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar/imunologia , Imuno-Histoquímica , Inflamação , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-13/imunologia , Interleucina-4/imunologia , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Ovalbumina/efeitos adversos , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pneumonia/patologia , Fator de Crescimento Transformador beta/imunologia
12.
Braz J Biol ; 83: e264570, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36651449

RESUMO

The constant intensification of aquaculture has considerable increased the stress levels of farmed fish and, consequently, the number and intensity of diseases outbreaks. Thus, studies on fish immune response, especially regarding the interaction of fish leukocytes with potential pathogens and xenobiotics are of great importance in order to develop new prophylactic and curative strategies. We isolated leukocytes from the head kidney of Astyanax lacustris-an important Neotropical fish species for aquaculture and a potential model for Neotropical aquaculture research-using a Percoll centrifugation protocol. The isolated leukocytes were incubated with lipopolysaccharide (LPS), and the expression of genes IL-1ß, IL-8, LysC, and LysG were measured. We assessed the phagocytotic activity of leukocytes using Congo red-dyed yeast, a novel and cost-effective protocol that has been developed in this study. The isolated leukocytes responded to LPS induction, exhibiting strong IL-1ß and IL-8 upregulation, two of the most important pro-inflammatory interleukins for vertebrates immune reponse. The optimal concentration of yeast for the phagocytic assay was 106 cells mL-1, resulting in acceptable phagocytic capacity (PC) but without excess of yeasts during the counting process, ensuring a high precision and accuracy of the method. To the best of our knowledge, the present study is the first to investigate the in vitro gene expression and phagocytic activity of leukocytes isolated from A. lacustris. Our findings will serve as a reference for future studies on the immunology and toxicology of Neotropical fish.


Assuntos
Characidae , Animais , Characidae/genética , Expressão Gênica , Interleucina-8/metabolismo , Leucócitos/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo
13.
Braz J Med Biol Res ; 56: e12547, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36995873

RESUMO

The main goal of this study was to determine whether oxidative imbalance mediated by AT1 receptor (AT1R) is responsible for deleterious endothelial responses to mental stress (MS) in overweight/obese class I men. Fifteen overweight/obese men (27±7 years old; 29.8±2.6 kg/m2) participated in three randomized experimental sessions with oral administration of the AT1R blocker olmesartan (40 mg; AT1R blockade) or ascorbic acid (AA; 3g) infusion or placebo [both intravenously (0.9% NaCl) and orally]. After two hours, endothelial function was determined by flow-mediated dilation (FMD) before (baseline), 30 min (30MS), and 60 min (60MS) after a five-minute acute MS session (Stroop Color Word Test). Blood was collected before (baseline), during MS, and 60 min after MS for redox homeostasis profiling: lipid peroxidation (TBARS; thiobarbituric acid reactive species), protein carbonylation, and catalase activity by colorimetry and superoxide dismutase (SOD) activity by an ELISA kit. At the placebo session, FMD significantly decreased 30MS (P=0.05). When compared to baseline, TBARS (P<0.02), protein carbonylation (P<0.01), catalase (P<0.01), and SOD (P<0.01) increased during the placebo session. During AT1R blockade, FMD increased 30 min after MS (P=0.01 vs baseline; P<0.01 vs placebo), while AA infusion increased FMD only 60 min after MS. No differences were observed during MS with the AT1R blockade and AA regarding TBARS, protein carbonylation, catalase, and SOD. AT1R-mediated redox imbalances played an important role in endothelial dysfunction to mental stress.


Assuntos
Obesidade , Estresse Psicológico , Humanos , Estresse Psicológico/patologia , Células Endoteliais/patologia , Estresse Oxidativo , Masculino , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Receptor Tipo 1 de Angiotensina/metabolismo
14.
Braz J Med Biol Res ; 56: e12533, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37585913

RESUMO

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.


Assuntos
Doenças Cardiovasculares , MicroRNAs , Ratos , Animais , Doenças Cardiovasculares/metabolismo , Miócitos Cardíacos/metabolismo , Ratos Wistar , Fator de Necrose Tumoral alfa/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo , Arginina/farmacologia , Arginina/metabolismo , Insulina , Frutose/metabolismo , Frutose/farmacologia , Suplementos Nutricionais , Hipertrofia/metabolismo , MicroRNAs/metabolismo
15.
bioRxiv ; 2023 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-37398065

RESUMO

Human pregnancy is frequently accompanied by nausea and vomiting that may become severe and life-threatening, as in hyperemesis gravidarum (HG), the cause of which is unknown. Growth Differentiation Factor-15 (GDF15), a hormone known to act on the hindbrain to cause emesis, is highly expressed in the placenta and its levels in maternal blood rise rapidly in pregnancy. Variants in the maternal GDF15 gene are associated with HG. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We found that the great majority of GDF15 in maternal circulation is derived from the feto-placental unit and that higher GDF15 levels in maternal blood are associated with vomiting and are further elevated in patients with HG. Conversely, we found that lower levels of GDF15 in the non-pregnant state predispose women to HG. A rare C211G variant in GDF15 which strongly predisposes mothers to HG, particularly when the fetus is wild-type, was found to markedly impair cellular secretion of GDF15 and associate with low circulating levels of GDF15 in the non-pregnant state. Consistent with this, two common GDF15 haplotypes which predispose to HG were associated with lower circulating levels outside pregnancy. The administration of a long-acting form of GDF15 to wild-type mice markedly reduced subsequent responses to an acute dose, establishing that desensitisation is a feature of this system. GDF15 levels are known to be highly and chronically elevated in patients with beta thalassemia. In women with this disorder, reports of symptoms of nausea or vomiting in pregnancy were strikingly diminished. Our findings support a causal role for fetal derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to GDF15, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.

16.
J Nanosci Nanotechnol ; 12(8): 6828-34, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22962830

RESUMO

Nanostructured silica based xerogels and aerogels are prepared by sol-gel technology, using methyltrimethoxysilane as precursor. The influence of the drying method and conditions on the microstructure of the obtained materials is investigated, since the drying stage has a critical influence on their porosity. Two types of drying methods were used: atmospheric pressure drying (evaporative), to produce xerogels, and supercritical fluids drying, to obtain aerogels. Although the supercritical fluids drying technique is more expensive and hazardous than the atmospheric pressure drying, it is well known that aerogels are less dense than the xerogels due to less pore shrinkage. However, the ideal situation would be to use atmospheric pressure drying in conditions that minimize the pore collapse. Therefore, in this work, different temperature cycles for atmospheric pressure drying and two heating rates for the supercritical fluids drying are tested to study the gels' shrinkage by analyzing the density and porosity properties of the final materials. The best materials obtained are aerogels dried with the lower heating rate (approximately 80 degrees C/h), since they exhibit very low bulk density (approximately 50 kg/m3), high porosity (95%)-mainly micro and mesopores, high surface area (approximately 500 m2/g), moderate flexibility and a remarkable hydrophobic character (>140 degrees). It was proved that the temperature cycles of atmospheric pressure drying can be tuned to obtain xerogels with properties comparable to those of aerogels, having a bulk density only approximately15 kg/m3 higher. All the synthesized materials fulfill the requirements for application as insulators in Space environments.

17.
J Clin Pharm Ther ; 37(4): 420-5, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22017324

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Some antimicrobial agents are active in vitro against Leptospiras. The use of penicillins at the late stage of leptospirosis is still controversial. We aimed to evaluate the use of penicillin in patients with leptospirosis-associated acute kidney injury (AKI). METHODS: A retrospective study was conducted of patients with leptospirosis admitted to two hospitals in Fortaleza city, Brazil, between 1985 and 2008. AKI was defined according to the RIFLE and AKIN classifications. Patients were divided in two groups according to whether they were treated with a penicillin or not. RESULTS: Two hundred and eighty-seven patients were included, with an average age of 36·8±15·6 years and mostly male (80·8%). One hundred and twelve patients (39%) received a penicillin. Patients treated with a penicillin were younger (32±14 years vs. 39±16 years, P=0·0002) and had a shorter hospital stay (8·4±5·0 vs. 11±7·7 days, P<0·0001). There was no difference in the onset of symptoms before hospital admission between the two groups (6·5±3·0 vs. 7·7±4·7, P=0·33). Systolic blood pressure was lower in the penicillin group (111±21 vs. 119±22 mmHg, P=0·04). AKI, need of dialysis and renal recovery at the time of hospital discharge were more frequent in patients who did not use a penicillin (P<0·05). Mortality was similar in both groups (11·6% vs. 13·7%, P=0·60). CONCLUSION: Treatment of leptospirosis with antibiotics, including the penicillin, remains controversial. The main benefit of using penicillin in the present study was a reduction in the length of hospital stay and fewer complications, such as AKI, but its use was not associated with a decrease in mortality. On balance of risks and benefits, we recommend the use of penicillin in late-stage leptospirosis.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Leptospirose/tratamento farmacológico , Penicilinas/uso terapêutico , Injúria Renal Aguda/microbiologia , Injúria Renal Aguda/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Feminino , Humanos , Tempo de Internação , Leptospirose/complicações , Leptospirose/mortalidade , Masculino , Pessoa de Meia-Idade , Penicilinas/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
19.
J Small Anim Pract ; 63(8): 624-631, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35244213

RESUMO

OBJECTIVES: The objective of this study was to compare waveforms obtained with a new device for the non-invasive monitoring of intracranial pressure (ICP) in dogs with and without neurological disease. MATERIALS AND METHODS: This prospective study was conducted on both neurologically normal dogs and dogs with neurological diseases. First, non-invasive ICP waveforms were recorded in normal dogs using the Braincare® BcMM 2000 monitor while the dogs were under general anaesthesia induced for procedures unrelated to this study. The dogs were positioned in lateral recumbency, and the sensor was placed over the skin of the parietal region. Secondly, non-invasive ICP waveforms were monitored in dogs with brain and spinal disease until waveforms with characteristic peaks were acquired. All the recorded signals were amplified, filtered and digitalized, by the device, and then transferred to a computer for analysis. RESULTS: Normal pulse waveforms indicating normal brain complacency were observed in eight neurologically normal dogs. In six dogs with brain disease, abnormal pulse waveforms were observed suggesting increased ICP and decreased brain complacency. Four dogs with spinal disease undergoing myelography, had normal waveforms before contrast medium injection and abnormal pulse waveforms during contrast medium injection, indicating a potential increase in ICP. CLINICAL SIGNIFICANCE: Based on these preliminary observations, this method was capable of detecting abnormal pulse waveforms that suggested increased ICP.


Assuntos
Doenças do Cão , Hipertensão Intracraniana , Doenças da Coluna Vertebral , Animais , Cães , Hipertensão Intracraniana/veterinária , Pressão Intracraniana , Monitorização Fisiológica/veterinária , Estudos Prospectivos , Doenças da Coluna Vertebral/veterinária
20.
Braz J Med Biol Res ; 55: e12110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35703682

RESUMO

In preparation for tracheal intubation during induction of anesthesia, the patient may be ventilated with 100% oxygen. To investigate the impact of acute isocapnic hyperoxia on endothelial activation and vascular remodeling, ten healthy young men (24±3 years) were exposed to 5-min normoxia (21% O2) and 10-min hyperoxia trials (100% O2). During hyperoxia, intercellular adhesion molecules (ICAM-1) (hyperoxia: 4.16±0.85 vs normoxia: 3.51±0.84 ng/mL, P=0.04) and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) (hyperoxia: 8.40±3.84 vs normoxia: 5.73±2.15 pg/mL, P=0.04) increased, whereas matrix metalloproteinase (MMP-9) activity (hyperoxia: 0.53±0.11 vs normoxia: 0.68±0.18 A.U., P=0.03) decreased compared to the normoxia trial. We concluded that even short exposure to 100% oxygen may affect endothelial activation and vascular remodeling.


Assuntos
Hiperóxia , Moléculas de Adesão Celular , Humanos , Masculino , Oxigênio , Consumo de Oxigênio/fisiologia , Remodelação Vascular
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