Publications by authors named "Natália Noronha"

30 Publications

  • Page 1 of 1

The Impact of Gastric Bypass on Telomere Length and Shelterin Complex Gene Expression: 6 Months Prospective Study.

Obes Surg 2021 Mar 18. Epub 2021 Mar 18.

Laboratory of Nutrigenomics Studies, Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.

Background: Telomeres are structures located at the ends of chromosomes associated with a protein complex, known as the shelterin complex. In individuals with obesity, excess adipose tissue plays a key role in inducing a chronic and systemic inflammatory state, which can cause TL shortening. In this context, bariatric surgery is one of the most effective treatment modalities in improving metabolic control.

Aim: Therefore, the present study aimed to evaluate how a short postoperative period of gastric bypass affects TL and expression of POT1, TRF1 and TRF2 genes.

Methods: Forty-eight women submitted to RYGB were evaluated before and after 6 months of the surgical procedure. Anthropometric measures of body weight and height (BMI), abdominal circumference (AC), body composition, food intake and blood collection for biochemical evaluation, TL analysis (DNA), and gene expression (RNA) were collected at each moment.

Results: There was a reduction of weight, BMI, AC, FM and FFM as well as of glycemia, total cholesterol, LDL-cholesterol, and triglycerides after gastric bypass. No difference in energy intake and macronutrients consumption was observed. There was no significant change in TL, but there was a significant increase of POT1 and TRF1 gene expression after surgery, while TRF2 expression did not change.

Conclusions: Despite bariatric surgery is not capable of increasing telomere length in a short-term period, no reduction is observed; additionally, we found a correlation between serum triglycerides concentration and TL. The increase of POT1 and TRF1 gene expression may explain the maintenance of the TL after 6 months postoperative period.
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http://dx.doi.org/10.1007/s11695-021-05299-9DOI Listing
March 2021

Antenatal Diagnosis of Double Aortic Arch.

Arq Bras Cardiol 2021 02;116(2 suppl 1):4-7

Bristol Royal Hospital for Children, Bristol - Reino Unido da Grã-Bretanha.

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http://dx.doi.org/10.36660/abc.20190310DOI Listing
February 2021

Beta-alanine fails to improve on 5,000 m running time despite increasing PAT1 expression in long-distance runners.

J Sports Med Phys Fitness 2020 Dec 11. Epub 2020 Dec 11.

Nutrigenomics Studies Laboratory, Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.

Background: Beta-alanine has become a dietary supplement widely used by athletes due to its ergogenic effect. However, there is still no consensus on the performance benefit of beta-alanine on exercise lasting longer than ten minutes. The present study aimed to evaluate the effect of beta-alanine supplementation on running performance and the expression of TauT and PAT1.

Methods: This double-blind, randomized study enrolled 16 long-distance runners (37 ± 8 years) who were randomly allocated to two groups: Placebo (PLA) and Beta-alanine (BA) (4.8 g·day-1) for four weeks. Maximal oxygen consumption, anthropometry, body composition, and food intake were determined. Before and after the intervention, the athletes undertook a 5,000 m running time trial. Venous blood (TauT and PAT1 expressions) and ear lobe capillary blood (lactate) collected before and after exercise. Between tests, we monitored the training variables.

Results: The results were analyzed by T-tests and an ANOVA of repeated measures, with Sidak's post hoc (p<0.05). PLA exhibited lower body fat than BA (8.7 ± 2.2 vs. 11.5 ± 2.8%, p=0.04). After supplementation, there was an increase in PAT1 expression in BA when compared to PLA (1.17 ± 0.47 vs. 0.77 ± 0.18, p=0.04). No significant differences were shown for the 5,000 m running time in PLA (PRE:1128 ± 72; POST:1123 ± 72s) and BA (PRE:1107 ± 95; POST:1093 ± 86s).

Conclusions: Although beta-alanine supplementation increased PAT1 expression, there was no statistically significant improvement in 5,000 m running performance. However, individual responses should be considered as the BA showed a higher delta than the PLA.
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http://dx.doi.org/10.23736/S0022-4707.20.11946-7DOI Listing
December 2020

Changes in DNA Methylation and Gene Expression of Insulin and Obesity-Related Gene after Roux-en-Y Gastric Bypass.

Int J Mol Sci 2020 Jun 24;21(12). Epub 2020 Jun 24.

Laboratory of Nutrigenomics Studies, Health Science Department, Ribeirão Preto Medical School, Ribeirão Preto 14049-900, Brazil.

Weight regulation and the magnitude of weight loss after a Roux-en-Y gastric bypass (RYGB) can be genetically determined. DNA methylation patterns and the expression of some genes can be altered after weight loss interventions, including RYGB. The present study aimed to evaluate how the gene expression and DNA methylation of , an obesity and insulin-related gene, change after RYGB. Blood samples were obtained from 13 women (35.9 ± 9.2 years) with severe obesity before and six months after surgical procedure. Whole blood transcriptome and epigenomic patterns were assessed by microarray-based, genome-wide technologies. A total of 1966 differentially expressed genes were identified in the pre- and postoperative periods of RYGB. From these, we observed that genes involved in obesity and insulin pathways were upregulated after surgery. Then, the gene was selected for further RT-qPCR analysis and cytosine-guanine nucleotide (CpG) sites methylation evaluation. We observed that the gene was upregulated, and six DNA methylation CpG sites were differently methylated after bariatric surgery. In conclusion, we found that RYGB upregulates genes involved in obesity and insulin pathways.
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http://dx.doi.org/10.3390/ijms21124476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352760PMC
June 2020

The effects of short-term combined exercise training on telomere length in obese women: a prospective, interventional study.

Sports Med Open 2020 Jan 16;6(1). Epub 2020 Jan 16.

Internal Medicine Department, Ribeirao Preto Medical School, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirão Preto, 14049-900, Brazil.

Background: Telomere length is inversely associated with the senescence and aging process. Parallelly, obesity can promote telomere shortening. Evidence suggests that physical activity may promote telomere elongation.

Objective: This study's objective is to evaluate the effects of combined exercise training on telomere length in obese women.

Design And Methods: Twenty pre-menopausal women (BMI 30-40 kg/m, 20-40 years) submitted to combined training (strength and aerobic exercises), but only 13 finished the protocol. Each exercise session lasted 55 min/day, three times a week, throughout 8 weeks. Anthropometric data, body composition, physical performance (Vo), and 8-h fasting blood samples were taken before and after 8 weeks of training. Leukocyte DNA was extracted for telomere length by RT-qPCR reaction, using the 2 methodology.

Results: After the training intervention, significant differences (p < 0.05) were observed in telomere length (respectively before and after, 1.03 ± 0.04 to 1.07 ± 0.04 T/S ratio), fat-free mass (46 ± 7 to 48 ± 5 kg), Vo (35 ± 3 to 38 ± 3 ml/kg/min), and waist circumference (96 ± 8 to 90 ± 6 cm). In addition, an inverse correlation between waist circumference and telomere length was found, before (r = - 0.536, p = 0.017) and after (r = - 0.655, p = 0.015) exercise training.

Conclusion: Combined exercise promoted leukocyte telomere elongation in obese women. Besides, the data suggested that greater waist circumference may predict shorter telomere length.

Clinical Trial Registration: ClinicalTrails.gov, NCT03119350. Retrospectively registered on 18 April 2017.
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http://dx.doi.org/10.1186/s40798-020-0235-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965549PMC
January 2020

Pulmonary sequestration: Two case reports.

Rev Port Cardiol 2019 08 3;38(8):611-612. Epub 2019 Nov 3.

Serviço de Cardiologia Pediátrica, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

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http://dx.doi.org/10.1016/j.repc.2018.09.013DOI Listing
August 2019

Association of MFSD3 promoter methylation level and weight regain after gastric bypass: Assessment for 3 y after surgery.

Nutrition 2020 02 25;70:110499. Epub 2019 Apr 25.

Laboratory of Nutrigenomics Studies, Department of Internal Medicine, Ribeirão Preto Medical School, University of Sao Paulo, Brazil. Electronic address:

Objectives: Genetic predisposition and epigenetic signatures could explain why some individuals regain the weight lost after different obesity treatments. Major facilitator superfamily domain 3 (MFSD3) is a family of membrane-bound solute carriers whose expression has been recently associated with nutrient intake and adipose tissue homeostasis. This study aimed to evaluate a possible association between MFSD3 preoperative methylation pattern and weight regain after bariatric surgery.

Methods: This is a longitudinal study comprising 24 obese (body mass index > 35 m/kg) women submitted to gastric bypass. Anthropometric measurements were evaluated at preoperative time and 1, 2, and 3 y after surgery, and then weight regain was calculated. Genomic DNA was extracted from leukocytes and was bisulfite modified by specific kits, according manufacturer's instructions. Methylation analysis was performed with the Infinium Human Methylation 450 K bead chip technology, and methylation level was expressed as a β value ranging from 0 (unmethylated) to 1 (fully methylated). Shapiro-Wilk, repeated-means analysis of variance, Spearman correlation, Mann-Whitney, and independent t tests were used in statistical analysis (P < 0.05).

Results: A total of 25% of patients regained significant weight. Weight regain after bariatric surgery was positively correlated with cg00010266 MFSD3 preoperative methylation levels (r = 0.6804, P = 0.0126). Moreover, cg00010266 MFSD3 baseline methylation levels were significantly higher in regainer patients than non-regainers (6.2 ± 1.5 versus 3.9 ± 1.2%, P = 0.026). Patients allocated in the higher cg00010266 MFSD3 preoperative methylation group had higher weight regain (4.1 ± 1.8 versus 6.7 ± 2.2 kg, P = 0.037).

Conclusions: Preoperative hypermethylation of MFSD3 gene is significantly associated with weight regain and a worse response to gastric bypass.
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http://dx.doi.org/10.1016/j.nut.2019.04.010DOI Listing
February 2020

Obesity, weight loss, and influence on telomere length: New insights for personalized nutrition.

Nutrition 2019 10 24;66:115-121. Epub 2019 May 24.

Department of Internal Medicine, Ribeirao Preto Medical School, University of São, Paulo, Ribeirão Preto, Brazil; Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address:

Telomeres are structures located at the ends of chromosomes associated with proteins, from the shelterin complex, which are responsible for the protection and preservation of the genetic material. The telomere length (TL) progressively decreases with each cell division, and recent evidence suggests that lifestyle can lead to telomere shortening. In individuals with obesity, excess adipose tissue plays a key role in inducing a chronic and systemic inflammatory state, which can cause TL shortening. Thus, the aim of the present review was to show the relationship between obesity and TL in addition to the possible risk factors for its shortening and how the different strategies for weight loss can modulate TL. As the crucial result, we can consider the association between TL and weight loss, and adiposity changes after different interventions, showing that TL may be used as a biomarker of responses to obesity treatment.
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http://dx.doi.org/10.1016/j.nut.2019.05.002DOI Listing
October 2019

Green tea supplementation improves oxidative stress biomarkers and modulates IL-6 circulating levels in obese women.

Nutr Hosp 2019 Jul;36(3):583-588

Ribeirão Preto Medical School. University of São Paulo.

Introduction: Introduction: obesity is associated with high levels of oxidative stress (OS) and inflammation. There is a lot of evidence that some polyphenols, such as green tea, have a positive impact on the OS state and consecutively, on inflammation. Objectives: the purposes of this study were: a) evaluate OS biomarkers in both obese and normal weight women; and b) evaluate if green tea supplementation has an impact on OS and inflammatory cytokine biomarkers of obese women. Methods: we evaluated obese (body mass index [BMI] ≥ 40 kg/m²) and normal weight (BMI between 18.5 and 24.9 kg/m²) women. Blood samples were used to access malondialdehyde (MDA), trolox equivalent antioxidant capacity (TEAC) and inflammatory cytokines. We randomly chose obese patients (18 individuals) and then gave them green tea supplementation for eight weeks. Statistical analysis included the Shapiro-Wilk, Wilcoxon, independent and paired t tests; p < 0.05 were considered as significant. Results: we enrolled 42 obese (BMI: 48.2 ± 9.3kg/m2) and 21 normal weight (BMI: 22.5 ± 2 kg/m2) women with an average age of 36.2 ± 9.1 years old. The serum levels of MDA were higher in obese (2.52 ± 0.31 µmol/l) than in eutrophic women (2.13 ± 0.26 µmol/l; p = 0.000). On the other hand, lower TEAC values were observed in the obese (0.75 ± 0.06 mM/l) than in the eutrophic group (0.78 ± 0.04 mM/l; p = 0.009). After the green tea intervention, MDA decreased 4.7% and TEAC increased 10%. Interleukin-6 (IL-6) serum levels decreased 12.7% after treatment (p = 0.03). Conclusions: a) the obese group had lower antioxidant capacity than eutrophic; and b) green tea supplementation ameliorated TEAC and MDA and reduced serum levels of IL-6 in obese women.
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http://dx.doi.org/10.20960/nh.2159DOI Listing
July 2019

Impact of green tea epigallocatechin-3-gallate on HIF1-α and mTORC2 expression in obese women: anti-cancer and anti-obesity effects?

Nutr Hosp 2019 Apr;36(2):315-320

Department of Internal Medicine. University of São Paulo.

Introduction: Introduction: epigallocatechin-3-gallate (EGCG) is the most abundant catechin contained in green tea (Camellia sinensis) and has been associated with anti-obesity and anti-cancer effects, but the exact molecular mechanisms remain elusive. In this context, this study was designed to improve the understanding of the EGCG anti-obesity and anti-cancer action. Objectives: this study was designed to examine the effects of EGCG on the expression of genes involved in obesity and cancer pathways in the peripheral blood mononuclear cells of obese women. Material and methods: this longitudinal interventional study enrolled eleven women with severe obesity that were submitted to eight weeks of green tea (decaffeinated green tea capsules with 450.7 mg of EGCG, two capsules/day) supplementation (intervention group) and ten eutrophic women as a control group. Weight (kg), body mass index (BMI, kg/m2), fat mass (kg) and gene expression (qPCR method) were assessed before and after supplementation. HIF1-alpha (HIF1-α), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and rapamycin-insensitive companion of mTOR (RICTOR) were selected as potential targets. Results: after supplementation, body weight (114.9 ± 14.3 versus 115 ± 13.8 kg), body mass index (44.1 ± 3.7 versus 44.1 ± 3.9 kg/m2) and fat mass (47.6 ± 3.3 versus 47.3 ± 3.4 kg) did not change. EGCG upregulated the RICTOR and HIF1-α expression, however, did not modify PI3K expression. Conclusion: this study demonstrated that EGCG has a potential role to obesity and cancer related to obesity control and can be used not only for the purpose of weight loss, but also for the improvement of obesity-related comorbidities.
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http://dx.doi.org/10.20960/nh.2216DOI Listing
April 2019

Severe iron-deficiency anemia as initial manifestation of pulmonary hemosiderosis in a child.

Einstein (Sao Paulo) 2018 Nov 29;16(4):eRC4505. Epub 2018 Nov 29.

Serviço de Pediatria Médica, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Idiopathic pulmonary hemosiderosis is a potentially fatal disease that results from episodes of alveolar hemorrhage of unknown origin. The clinical spectrum is varied, and anemia may constitute the only manifestation of illness, preceding other signs and symptoms by several months. We present the case of a 4 year-old child presenting with fever, vomiting and prostration, associated with pallor. He had microcytic and hypochromic anemia refractory to iron therapy. Gastrointestinal bleeding was ruled out after negative extensive etiological investigation. Subsequently, pulmonary infiltrates suggestive of alveolar hemorrhage were observed in the chest radiography. The cytological exam of the bronchoalveolar lavage showed hemosiderin-laden macrophages. After the etiological study, the diagnosis of idiopathic pulmonary hemosiderosis was made by exclusion. He was initiated on corticosteroid therapy, later associated to an immunosuppressive agent, with subsequent correction of anemia and of the radiological pattern. The patient is currently asymptomatic.
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http://dx.doi.org/10.31744/einstein_journal/2018RC4505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276813PMC
November 2018

Green tea supplementation promotes leukocyte telomere length elongation in obese women.

Nutr Hosp 2018 Jun 10;35(3):570-575. Epub 2018 Jun 10.

.

Introduction: inflammation and oxidative stress are factors that may play a substantial role in telomere attrition. In line of this, obesity is associated with telomere shortening. Green tea had anti-inflammatory and antioxidant effects and may alter telomere length (TL).

Objectives: we evaluated the effect of decaffeinated green tea supplementation in obese women on TL.

Methods: we conducted a cross-sectional interventional study with ten obese (body mass index [BMI] > 40 kg/m²) and eight normal weight (BMI > 18.5 and < 24.9 kg/m²) women (age between 27 and 48 years). The supplementation was carried out with capsules (each contained 450.7 mg of epigallocatechin-3-gallate) during eight weeks. Anthropometric and dietary intake assessment, and blood collection (for biochemical and TL analysis by quantitative PCR) were performed before and after supplementation. Normal weight patients were evaluated at a single moment.

Results: we observed a significant increase on TL after supplementation (1.57 ± 1.1 to 3.2 ± 2.1 T/Sratio; p < 0.05). Moreover, we found shorter TL in obese patients (day 0) when compared to normal weight individuals (3.2 ± 1.9 T/Sratio; p < 0.05) and an inverse association between TL and BMI, even after age adjustment (beta = -0.527; r² = 0.286; IC = -0.129, -0.009).

Conclusion: obesity is related to shorter telomeres. Green tea supplementation during eight weeks promotes telomere elongation in obese women.
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http://dx.doi.org/10.20960/nh.1392DOI Listing
June 2018

Importance of ambulatory blood pressure monitoring in the diagnosis and prognosis of pediatric hypertension.

Rev Port Cardiol 2018 09 2;37(9):783-789. Epub 2018 Jun 2.

Serviço de Cardiologia Pediátrica, Hospital Pediátrico de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

The prevalence of high blood pressure (BP) at pediatric age has increased progressively, one of the causes of which is obesity. However, the dominant etiology in this age group is renal and/or cardiovascular pathology. Ambulatory blood pressure monitoring (ABPM) is the method of choice for the diagnosis of hypertension, especially in children at high cardiovascular risk. Its use is limited to children from five years of age. Choosing appropriate cuff size is key to obtaining correct blood pressure. The main indication for ABPM is to confirm the diagnosis of hypertension. It also allows the diagnosis of white coat hypertension (which may represent an intermediate stage between the normotensive phase and hypertension), or masked hypertension, associated with progression to sustained hypertension and left ventricular hypertrophy (LVH). Children with isolated nocturnal hypertension should be considered as having masked hypertension. BP load is defined as the percentage of valid measurements above the 95th percentile for age, gender, and height. Values above 25-30% are pathological and those above 50% are predictive of LVH. ABPM correlates with target organ damage, particularly LVH and renal damage. It is useful in the differentiation of secondary hypertension, since these children show higher BP load and less nocturnal dipping, and confirmation of response to therapy. Thus ABPM allows the diagnosis and classification of hypertension, provides cardiovascular prognostic information and identifies patients with intermediate phenotypes of hypertension.
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http://dx.doi.org/10.1016/j.repc.2017.09.026DOI Listing
September 2018

Unusual cause of left ventricular dysfunction in a child.

Rev Port Cardiol 2019 02 21;38(2):159.e1-159.e5. Epub 2018 May 21.

Centro de Cirurgia Cardiotorácica, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery is a rare congenital heart disease and a cause of myocardial ischemia during childhood. Most undiagnosed cases die in the first year of life as an extensive collateral network is essential for survival. The diagnosis requires a high index of clinical suspicion. The authors present the case of an 8-year-old black asymptomatic child referred from Cape Verde Island in order to clarify left ventricular dilatation and dysfunction with systo-diastolic turbulent flows observed at the interventricular septum. At the age of 3 months, she was diagnosed with heart failure, in the context of showing dilated cardiomyopathy. She was managed and clinically improved with anticongestive therapy, which she was still taking at the time of admission to our Center. The echocardiogram findings suggested Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery and the diagnosis was confirmed by computerized angiotomography and cardiac catheterization. The patient was successfully submitted to direct implantation of the left coronary artery into the aorta, allowing the creation of a double coronary perfusion system. This case illustrates an unusual presentation of a rare pathology that survived without a diagnosis after the first year of life. It also reinforces the importance of multimodality image screening in these cases.
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http://dx.doi.org/10.1016/j.repc.2017.07.017DOI Listing
February 2019

Mammalian target of rapamycin complex 2 signaling in obese women changes after bariatric surgery.

Nutrition 2018 10 21;54:94-99. Epub 2018 Mar 21.

Department of Internal Medicine, Ribeirao Preto Medical School of University of Sao Paulo, Sao Paulo, Brazil. Electronic address:

Objectives: After bariatric surgery, modifications to signaling pathway networks including those of the metabolic regulator called mammalian or mechanistic target of rapamycin (mTOR) may lead to molecular alterations related to energy source availability, systemic nutrients, and catabolic and anabolic cellular processes. This study aimed to identify gene expression changes with regard to the mTOR complex 2 subunit signaling pathway in obese patients before and after bariatric surgery.

Methods: The experimental group included 13 obese women who were examined before (preoperative) and 6 mo after (postoperative) Roux-en-Y gastric bypass (RYGB) surgery. The control group included nine apparently eutrophic women matched by age and without any other metabolic diseases (i.e., no diabetes and no liver or kidney diseases). Peripheral blood mononuclear cell samples were collected for RNA extraction and subsequent microarray analysis.

Results: After this methodological procedure, we identified 47 000 differentially expressed genes. A subsequent bioinformatic analysis showed that three diferentially expressed genes (rapamycin-insensitive companion of mTOR [RICTOR], phosphoinositide-3-kinase regulatory subunit 1 [PIK3 R1], and hypoxia inducible factor 1 alpha subunit 1A [HIF1 A]) participated in the mTOR signaling pathway. Real-time quantitative polymerase chain reaction revealed that RICTOR, PIK3 R1, and HIF1 A were upregulated 6 mo after RYGB surgery (P <0.05). In addition, patients in the experimental group lost weight significantly and presented significant improvement in biochemical/metabolic variables.

Conclusions: The weight loss that was induced by RYGB surgery alters the mTOR signaling pathway and specifically the mTOR complex 2 subunit. The increased expression of genes that act in this pathway such as RICTOR, PIK3 R1, and HIF1 A reflects the induced weight loss and improved metabolic indicators (e.g., insulin resistance and lipolysis) that are evidenced in this study.
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http://dx.doi.org/10.1016/j.nut.2018.02.016DOI Listing
October 2018

Abdominal pain of cardiovascular origin.

Rev Port Cardiol 2018 May 26;37(5):449.e1-449.e4. Epub 2018 Apr 26.

Hospital Pediátrico de Coimbra, Serviço de Cardiologia Pediátrica, Coimbra, Portugal.

Infective endocarditis is a microbial infection of the endocardium and it is rare in the pediatric population. In children, congenital heart disease is one of the most important risk factors for developing infective endocarditis and can involve other structures in addition to cardiac valves. The prognosis is generally better than in other forms of endocarditis, although the average mortality rate in the pediatric population is 15-25%. Clinical manifestations can mimic other diseases such as meningitis and collagen-vascular disease or vasculitis. Therefore, a high degree of suspicion is required to make an early diagnosis. Gram-positive bacteria, specifically alpha-hemolytic streptococci, Staphylococcus aureus and coagulase-negative staphylococci, are the most commonly involved bacteria. Diagnosis is based on the modified Duke criteria, which rely mostly on clinical assessment, echocardiography and blood cultures. Antibacterial treatment should ideally be targeted. However, if no specific bacteria have been identified, patients should promptly be treated empirically with multiple drug regimens based on local resistance and the most common etiologies. The authors describe a case of a seven-year-old girl with classic clinical signs of endocarditis, with a clinical twist.
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http://dx.doi.org/10.1016/j.repc.2017.06.023DOI Listing
May 2018

Rare forms of pediatric congenital right ventricular fistulae.

Rev Port Cardiol 2018 May 21;37(5):453-454. Epub 2018 Apr 21.

Serviço de Cardiologia Pediátrica, Hospital Pediátrico de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

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http://dx.doi.org/10.1016/j.repc.2017.01.015DOI Listing
May 2018

A new resting metabolic rate equation for women with class III obesity.

Nutrition 2018 05 11;49:1-6. Epub 2017 Dec 11.

Department of Internal Medicine, University of Sao Paulo School of Medicine, Ribeirao Preto Campus, Ribeirao Preto, SP, Brazil. Electronic address:

Objective: Resting metabolic rate (RMR) is an important parameter to guide the nutritional therapy of class III obese patients. The aims of the present study were to develop a predictive equation for RMR estimation in class III obese women using anthropometric indicators and to compare indirect calorimetry with other predictive equations.

Methods: This was a cross-sectional study on women with class III obesity (body mass index >40 kg/m). Weight, height, fat-free mass, fat mass, and RMR of all individuals were measured. Multiple linear regression was used to determine the new RMR equation and the Bland-Altman plot was used to analyze the agreement between indirect calorimetry and the results of predictive equations.

Results: We evaluated 101 women with obesity class III and a mean age of 36.3 ± 10 y. The anthropometric and body composition variables used in the new equation had a coefficient of determination of 0.80, and a significant influence on RMR (P = 0.01). Harris-Benedict and World Health Organization equations showed similar bias and limits (181.6, +2 SD = 765.5, -2 SD = -402.2; 156.4, +2 SD = 799.4, -2 SD = -486.6, respectively). The Mifflin-St Jeor and Owen equations showed large clinical bias (mean, 239.2 and 463.9, respectively), and a tendency to overestimate RMR.

Conclusion: The prediction equations tested in the study had low accuracy in estimating RMR of women with class III obesity. However, our equation was developed specifically for this population, using variables known to influence their energy expenditure.
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http://dx.doi.org/10.1016/j.nut.2017.11.024DOI Listing
May 2018

Green tea supplementation upregulates uncoupling protein 3 expression in severe obese women adipose tissue but does not promote weight loss.

Int J Food Sci Nutr 2018 Dec 26;69(8):995-1002. Epub 2018 Feb 26.

a Department of Internal Medicine , Ribeirao Preto Medical School, University of São Paulo , Ribeirão Preto , Brazil.

This study aims (i) to verify expression of the UCPs, PLIN1, PPARG2, and ADRB3 genes in the abdominal subcutaneous adipose tissue of obese women at baseline and after 8 weeks of supplementation with decaffeinated green tea extract, and (ii) to associate findings with clinical parameters. This is a longitudinal study during which 11 women with obesity grade III were submitted to supplementation with 450 mg of (-)-epigallocatechin gallate (EGCG) (intervention group); the control group consisted of 10 eutrophic women. Anthropometric parameters [weight, height, and body mass index (BMI)], resting metabolic rate (RMR, measured by indirect calorimetry), and gene expression (measured by real-time PCR, RT-qPCR) were determined before and after supplementation. After 8 weeks, clinical parameters and UCP1, PLIN1, PPARG2, and ADRB3 expression remained unaltered in the intervention group (p > .05). Genetic analysis also showed that the UCP3 gene was upregulated (p = .026), but its upregulation did not promote weight loss.
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http://dx.doi.org/10.1080/09637486.2018.1442819DOI Listing
December 2018

Infant heart tumour.

Rev Port Cardiol 2018 Jan 26;37(1):93-94. Epub 2017 Dec 26.

Hospital Pediátrico de Coimbra, Serviço de Cardiologia Pediátrica, Coimbra, Portugal.

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http://dx.doi.org/10.1016/j.repc.2017.02.019DOI Listing
January 2018

Changes in Global Transcriptional Profiling of Women Following Obesity Surgery Bypass.

Obes Surg 2018 Jan;28(1):176-186

Department of Internal Medicine, Laboratory of Nutrigenomic Studies, Ribeirao Preto Medical School, FMRP, University of Sao Paulo, USP, Av Bandeirantes, 3900, Monte Alegre, Ribeirao Preto, SP, 14049-900, Brazil.

Background: Differential gene expression in peripheral blood mononuclear cells (PBMCs) after Roux-en-Y gastric bypass (RYGB) is poorly characterized. Markers of these processes may provide a deeper understanding of the mechanisms that underlie these events. The main goal of this study was to identify changes in PBMC gene expression in women with obesity before and 6 months after RYGB-induced weight loss.

Methods: The ribonucleic acid (RNA) of PBMCs from 13 obese women was analyzed before and 6 months after RYGB; the RNA of PBMCs from nine healthy women served as control. The gene expression levels were determined by microarray analysis. Significant differences in gene expression were validated by real-time quantitative polymerase chain reaction (RT-qPCR).

Results: Microarray analysis for comparison of the pre- and postoperative periods showed that 1366 genes were differentially expressed genes (DEGs). The main pathways were related to gene transcription; lipid, energy, and glycide metabolism; inflammatory and immunological response; cell differentiation; oxidative stress regulation; response to endogenous and exogenous stimuli; substrate oxidation; mTOR signaling pathway; interferon signaling; mitogen-activated protein kinases (MAPK), cAMP response element binding protein (CREB1), heat shock factor 1 (HSF1), and sterol regulatory element binding protein 1c (SREBP-1c) gene expression; adipocyte differentiation; and methylation.

Conclusions: Six months after bariatric surgery and significant weight loss, many molecular pathways involved in obesity and metabolic diseases change. These findings are an important tool to identify potential targets for therapeutic intervention and clinical practice of nutritional genomics in obesity.
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http://dx.doi.org/10.1007/s11695-017-2828-xDOI Listing
January 2018

Complement factor B mutation-associated aHUS and myocardial infarction.

BMJ Case Rep 2017 Jul 14;2017. Epub 2017 Jul 14.

Serviáo de Cuidados Intensivos Pediátricos, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal.

A 6-month-old female infant was referred with a 3-day history of low-grade fever, slight nasal congestion and rhinorrhoea. On admission, the clinical findings were unremarkable and she was discharged home. However, she became progressively more listless with a decreased urine output and was once again seen in the emergency department. Analytically she was found to have metabolic acidosis, hyperkalaemia, thrombocytopaenia, anaemia and schistocytes in the peripheral blood smear. Based on these findings, the diagnosis of haemolyticâ-uremic syndrome was made. A few hours postadmission, there was an abrupt clinical deterioration. She went into cardiorespiratory arrest and she was successfully resuscitated. An ST-segment elevation was noted on the ECG monitor and the troponin I levels were raised, suggesting myocardial infarction. Despite intensive supportive therapy, she went into refractory shock and died within 30 hours.
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http://dx.doi.org/10.1136/bcr-2017-219716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534890PMC
July 2017

Influence of expression of UCP3, PLIN1 and PPARG2 on the oxidation of substrates after hypocaloric dietary intervention.

Clin Nutr 2018 08 15;37(4):1383-1388. Epub 2017 Jun 15.

Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address:

Background & Aims: In addition to environmental and psychosocial factors, it is known that genetic factors can also influence the regulation of energy metabolism, body composition and determination of excess weight. The objective of this study was to evaluate the influence of UCP3, PLIN1 and PPARG2 genes on the substrates oxidation in women with grade III obesity after hypocaloric dietary intervention.

Subjects/methods: This is a longitudinal study with 21 women, divided into two groups: Intervention Group (G1): 11 obese women (Body Mass Index (BMI) ≥40 kg/m), and Control Group (G2): 10 eutrophic women (BMI between 18.5 kg/m and 24.9 kg/m). Weight (kg), height (m), BMI (kg/m), substrate oxidation (by Indirect Calorimetry) and abdominal subcutaneous adipose tissue were collected before and after the intervention. For the dietary intervention, the patients were hospitalized for 6 weeks receiving 1200 kcal/day.

Results: There was a significant weight loss (8.4 ± 4.3 kg - 5.2 ± 1.8%) and reduction of UCP3 expression after hypocaloric dietary intervention. There was a positive correlation between carbohydrate oxidation and UCP3 (r = 0.609; p = 0.04), PLIN1 (r = 0.882; p = 0.00) and PPARG2 (r = 0.791; p = 0.00) expression before dietary intervention and with UCP3 (r = 0.682; p = 0.02) and PLIN1 (r = 0.745; p = 0.00) genes after 6 weeks of intervention. There was a negative correlation between lipid oxidation and PLIN1 (r = -0.755; p = 0.00) and PPARG2 (r = 0.664; p = 0.02) expression before dietary intervention and negative correlation with PLIN1 (r = 0.730; p = 0.02) expression after 6 weeks of hypocaloric diet.

Conclusion: Hypocaloric diet reduces UCP3 expression in individuals with obesity and the UCP3, PLIN1 and PPARG2 expression correlate positively with carbohydrate oxidation and negatively with lipid oxidation.
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http://dx.doi.org/10.1016/j.clnu.2017.06.012DOI Listing
August 2018

Comparison of gene expression profile between blood cells and white adipose tissue of patients with obesity

Nutr Hosp 2017 06 5;34(3):608-612. Epub 2017 Jun 5.

University of Sao Paulo.

Introduction: Gene expression analyses from peripheral blood mononuclear cells (PBMC) and white adipose tissue are conflicting. It seems that results from single tissue are not enough to explain how changes affect humans as a complex biological system.

Objective: The aim of this study was to compare, from obesity subjects, PBMC and white adipose tissue gene expression that regulates adipogenesis (perilipin 1 [PLIN1], adrenoreceptor beta 3 [ADRB3] and peroxisome proliferator-activated receptor [PPARG2]) and the energy metabolism (uncoupling protein UCP1, UCP2 and UCP3) process.

Methods: This study enrolled 35 obese patients, with a body mass index (BMI) > 40 kg/m2 (obesity group [OG]), and ten eutrophic health subjects, 18 > BMI > 24.9 kg/m2 (control group [CG]). Anthropometric and body composition data were assessed at recruitment using standardized protocols. Samples of peripheral blood and subcutaneous adipose tissue (biopsy) were collected to analyze gene expression by RT-qPCR technique. For statistical analysis, we used the Shapiro-Wilk test and Wilcoxon tests by the SPSS software version 20.0; a p < 0.05 significance level was adopted.

Results: There were significant differences of PLIN1, ADRB3, PPARG2 and UCP3 expression between blood against adipose tissue samples, showing that these genes are upregulated in adipose tissue. UCP2 expression was upregulated in PBMC.

Conclusion: The PLIN1, ADRB3, PPARG2 and UCP3 genes were preferentially expressed in adipose tissue. However, UCP2 was upregulated in PBMC, suggesting that this gene may be assessed in a peripheral blood cell, which is easily accessible, safe and practical.
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http://dx.doi.org/10.20960/nh.438DOI Listing
June 2017

Incidental finding in a newborn with respiratory distress.

Einstein (Sao Paulo) 2017 Jul-Sep;15(3):378-379. Epub 2017 Jun 12.

Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

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http://dx.doi.org/10.1590/S1679-45082017AI4001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823058PMC
May 2018

UCP2 and PLIN1 Expression Affects the Resting Metabolic Rate and Weight Loss on Obese Patients.

Obes Surg 2017 02;27(2):343-348

Department of Internal Medicine, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Avenida dos Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil.

Background: Analysis of the expression of genes related to the energy metabolism can elucidate the understanding of physiological and genetic factors that contribute to obesity. This study aimed to evaluate the expression of genes and its influence on resting metabolic rate and weight loss in obese patients before and after bariatric surgery.

Methods: This study was conducted on 23 women, who were divided into two groups: bariatric surgery (preoperative and 6 months after surgery) and control. Abdominal subcutaneous adipose tissue samples were collected to analyze the gene expression, and the resting metabolic rate (RMR) was measured by indirect calorimetry.

Results: Significant differences were observed in weight reduction (22 %, p = 0.01), BMI (22.5 %, p = 0.01), and RMR values (10.5 %, p = 0.01) after the bariatric surgery, while the weight-adjusted RMR increased (15.8 %, p = 0.01). Increased UCP2 expression after 6 months of Roux-en-Y gastric bypass (RYGB) as compared to preoperative period (0.764 to 1.268, p = 0.01) was observed. Analysis with weight-adjusted RMR as dependent variable revealed that UCP2 (r  = 0.517, p = 0.01) and PLIN1 (r  = 0.420, p = 0.04) expression determine the RMR values in preoperative period. Moreover, UCP2 and PLIN1 expression in preoperative period influenced the percentage of weight loss, even when adjusted for age and BMI.

Conclusions: We have demonstrated that after 6 months of bariatric surgery, there is significant increase in the UCP2 expression. Additionally, the expression of UCP2 and PLIN1 genes influences the resting metabolic rate in obese individuals and could predict the weight loss after bariatric surgery.
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http://dx.doi.org/10.1007/s11695-016-2275-0DOI Listing
February 2017

[Risk Factors for Healthcare Associated Sepsis in Very Low Birth Weight Infants].

Acta Med Port 2016 Apr 29;29(4):261-7. Epub 2016 Apr 29.

Serviço de Pediatria. Hospital Pediátrico de Coimbra: Centro Hospital e Universitário de Coimbra. Coimbra.

Introduction: Healthcare associated infections in very low birth weight infants are associated with significant morbidity and mortality and are also a cause of increased length of stay and hospital costs. The objective of this study was to evaluate the rate of healthcare-associated sepsis and associated risk factors in very low birth weight infants.

Material And Methods: Retrospective observational study including very low birth weight infants hospitalized in a Neonatal Intensive Care Unit during ten years (2005-2014). We evaluated the association between several risk factors and healthcare-associated sepsis.

Results: 461 very low birth weight infants were admitted. There were 110 episodes of HS in 104 very low birth weight infants and 53 episodes of sepsis associated with central vascular catheter. The density of the sepsis was 7.5/1 000 days of hospitalization and the density of central vascular catheter - associated sepsis was 22.6/1 000 days of use. The infants with HS had lower average birth weight and gestational age (959 ± 228 g vs 1191 ± 249 g and 27.6 ± 2 vs 29.8 ± 2.2 weeks), p < 0.001. After adjusting for birth weight and gestational age we verified an association between healthcare-associated sepsis and antibiotic therapy in D1, the duration of parenteral nutrition and central vascular catheter. After logistic regression only the gestational age and duration of parenteral nutrition remained as independent significant risk factors for healthcare-associated sepsis.

Discussion: The independent factors for healthcare-associated sepsis are gestational age and duration of parenteral nutrition.

Conclusion: For each extra week on gestational age the risk declined in 20% and for each day of NP the risk increased 22%.
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http://dx.doi.org/10.20344/amp.6839DOI Listing
April 2016

UCP1 and UCP3 Expression Is Associated with Lipid and Carbohydrate Oxidation and Body Composition.

PLoS One 2016 9;11(3):e0150811. Epub 2016 Mar 9.

Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto-SP, Brazil.

Background/objective: Uncoupling proteins (UCPs) are located in the inner membrane of mitochondria. These proteins participate in thermogenesis and energy expenditure. This study aimed to evaluate how UCP1 and UCP3 expression influences substrate oxidation and elicits possible changes in body composition in patients submitted to bariatric surgery.

Subjects/methods: This is a longitudinal study comprising 13 women with obesity grade III that underwent bariatric surgery and 10 healthy weight individuals (control group). Body composition was assessed by bioelectrical impedance. Carbohydrate and fat oxidation was determined by indirect calorimetry. Subcutaneous adipose tissue was collected for gene expression analysis. QPCR was used to evaluate UCP1 and UCP3 expression.

Results: Obese patients and the control group differed significantly in terms of lipid and carbohydrate oxidation. Six months after bariatric surgery, the differences disappeared. Lipid oxidation correlated with the percentage of fat mass in the postoperative period. Multiple linear regression analysis showed that the UCP1 and UCP3 genes contributed to lipid and carbohydrate oxidation. Additionally, UCP3 expression was associated with BMI, percentage of lean body mass, and percentage of mass in the postoperative period.

Conclusions: UCP1 and UCP3 expression is associated with lipid and carbohydrate oxidation in patients submitted to bariatric surgery. In addition, UCP3 participates in body composition modulation six months postoperatively.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150811PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784729PMC
July 2016

The painted shoes.

BMJ Case Rep 2015 Sep 3;2015. Epub 2015 Sep 3.

Emergency Department and Infectious Disease Service, Hospital Pediátrico, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal.

A previously well 4-year-old boy presented to the emergency room with progressive cyanosis, pallor and vomiting over the last 5 h. Oxygen saturation on pulse oximetry was 87-89% despite 9 L/min of supplemental oxygen. He was tachypnoeic and had a systolic heart murmur, with no other findings on clinical examination. In his medical history, there was record of a restrictive atrial septal defect, with a normal echocardiogram from 3 years before. He had no relevant family history. His shoes appeared to have been recently painted, which raised the suspicion of methaemoglobinaemia, presumptively caused by aniline-containing shoe dye. The shoes were removed promptly and his feet washed profusely. After confirming the diagnosis, methylene blue was started. The level of methaemoglobin decreased rapidly and the boy made a full recovery.
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http://dx.doi.org/10.1136/bcr-2015-210619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567729PMC
September 2015