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Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated the proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, the 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72 h of cultivation. The analysis of the mean proliferation index (PI) showed a trend for a significant difference between the 45,X and 46,X+der(X)/der(Y) cell lineages; however, there were no intra-individual differences. On the other hand, mean SCE frequencies showed that 46,X+der(X) had the highest mean value and 46,XX the lowest, with 45,X occupying an intermediate position among the lineages found in at least three participants; moreover, there were intra-individual differences in five patients. Although 46,X+der(X)/der(Y) cell lineages, found in more than 70% of participants, were the most unstable, they had a slightly higher mean PI than the 45,X cell lineages in younger (≤17 years) mosaic TS participants. This suggests that cells with a karyotype distinct from 45,X may increase with time in mosaic TS children and adolescents.
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PURPOSE OF REVIEW: The Amazon region has a high biodiversity of flora, with an elevated variety of fruits, such as Camu-Camu (Myrciaria dúbia), Açaí (Euterpe oleracea Mart.), Tucumã (Astrocaryum aculeatum and Astrocaryum vulgare), Fruta-do-conde (Annona squamosa L.), Cupuaçu (Theobroma grandiflorum), Graviola (Annona muricata L.), Guarana (Paullinia cupana Kunth var. sorbilis), and Pitanga (Eugenia uniflora), among many others, that are rich in phytochemicals, minerals and vitamins with prominent antioxidant and anti-inflammatory potential. RECENT FINDINGS: Studies evaluating the chemical composition of these fruits have observed a high content of nutrients and bioactive compounds. Such components are associated with significant biological effects in treating various non-communicable diseases (NCDs) and related complications. Regular intake of these fruits from Amazonas emerges as a potential therapeutic approach to preventing and treating NCDs as a nutritional strategy to reduce the incidence or mitigate common complications in these patients, which are the leading global causes of death. As studies remain largely unexplored, this narrative review discusses the possible health-beneficial effects for patients with NCDs.
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Frutas , Doenças não Transmissíveis , Humanos , Euterpe/química , Antioxidantes/farmacologia , Compostos Fitoquímicos/farmacologia , Brasil , Annona/química , Anti-Inflamatórios/farmacologiaRESUMO
Background: Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes. Methods: In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems. Results: Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in MYH7 (n=60, 11.2%) and MYBPC3 (n=41, 7.7%) were the most common HCM variants. The HCM phenocopy variants included variants in the TTR (n=7, 1.3%) and GLA (n=2, 0.4%) genes. The mean (standard deviation) ages of patients with HCM or HCM phenocopy variants, including TTR and GLA variants, were 42.8 (17.9), 54.6 (17.0), and 69.0 (1.4) years, respectively. Conclusions: The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA (TTR variants) and FD (GLA variants), which are treatable disorders, in the differential diagnosis of patients with increased LVWT of unknown etiology.
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Sulforaphane (SFN), found in cruciferous vegetables, is a known activator of NRF2 (master regulator of cellular antioxidant responses). Patients with chronic kidney disease (CKD) present an imbalance in the redox state, presenting reduced expression of NRF2 and increased expression of NF-κB. Therefore, this study aimed to evaluate the effects of SFN on the mRNA expression of NRF2, NF-κB and markers of oxidative stress in patients with CKD. Here, we observed a significant increase in the mRNA expression of NRF2 (p = 0.02) and NQO1 (p = 0.04) in the group that received 400 µg/day of SFN for 1 month. Furthermore, we observed an improvement in the levels of phosphate (p = 0.02), glucose (p = 0.05) and triglycerides (p = 0.02) also in this group. On the other hand, plasma levels of LDL-c (p = 0.04) and total cholesterol (p = 0.03) increased in the placebo group during the study period. In conclusion, 400 µg/day of SFN for one month improves the antioxidant system and serum glucose and phosphate levels in non-dialysis CKD patients.
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Isotiocianatos , NAD(P)H Desidrogenase (Quinona) , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , RNA Mensageiro , Insuficiência Renal Crônica , Sulfóxidos , Humanos , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Feminino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Glicemia/metabolismo , Regulação para Cima/efeitos dos fármacos , Adulto , Idoso , NF-kappa B/metabolismo , NF-kappa B/genéticaRESUMO
PURPOSE OF REVIEW: This narrative review will discuss how the intake of specific protein sources (animal and vegetable) providing specific amino acids can modulate the gut microbiota composition and generate toxins. A better understanding of these interactions could lead to more appropriate dietary recommendations to improve gut health and mitigate the risk of complications promoted by the toxic metabolites formed by the gut microbiota. RECENT FINDINGS: Gut microbiota is vital in maintaining human health by influencing immune function and key metabolic pathways. Under unfavorable conditions, the gut microbiota can produce excess toxins, which contribute to inflammation and the breakdown of the integrity of the intestinal barrier. Genetic and environmental factors influence gut microbiota diversity, with diet playing a crucial role. Emerging evidence indicates that the gut microbiota significantly metabolizes amino acids from dietary proteins, producing various metabolites with beneficial and harmful effects. Amino acids such as choline, betaine, l-carnitine, tyrosine, phenylalanine, and tryptophan can increase the production of uremic toxins when metabolized by intestinal bacteria. The type of food source that provides these amino acids affects the production of toxins. Plant-based diets and dietary fiber are associated with lower toxin formation than animal-based diets due to the high amino acid precursors in animal proteins.
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Aminoácidos , Proteínas Alimentares , Microbioma Gastrointestinal , Humanos , Proteínas Alimentares/metabolismo , Aminoácidos/metabolismo , Dieta , Animais , Toxinas Urêmicas , Fibras na Dieta , Proteínas de Vegetais Comestíveis , Toxinas BiológicasRESUMO
Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines.
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Introduction Turner syndrome (TS) affects â¼ 1 in 2,500 live births. The presence of hearing alterations is one of the comorbidities found in this syndrome. Objective The present study aimed to evaluate the central auditory abilities in TS and to associate the alterations found with the cytogenetic pattern of the syndrome. Methods We included children and adults aged 9 to 39 years old, diagnosed with TS, with numerical or structural alterations of sex chromosomes in their karyotype. A battery of behavioral tests of central auditory processing (CAP) was performed, including a test within the modalities: monoaural low-redundancy, dichotic listening, binaural interaction, and temporal processing (resolution and ordering). We studied auditory skills in the total sample and in the sample stratified by age, divided into groups: G1 (9 to 13 years old), G2 (14 to 19 years old), and G3 (20 to 31 years old). For the association of the cytogenetic pattern, the division was T1 (chromosome monosomy X), and T2 (other TS cytogenetic patterns). Statistical analysis presented data expressed as median and interquartile range for numerical data and as frequency and percentage for categorical data. Results We found alterations in four auditory skills in the three age groups, but there was a statistically significant difference between the age groups only in the Gaps in Noise Test (GIN) ( p -value = 0.009). Regarding karyotype, a greater number of alterations in the T1 cytogenetic pattern (chromosome monosomy X) was observed in four auditory skills, but without a statistically significant difference. Conclusion The alterations found point to an impairment in CAP in TS.
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BACKGROUND: Disease-related variants in PHEX cause XLH by an increase of fibroblast growth factor 23 (FGF23) circulating levels, resulting in hypophosphatemia and 1,25(OH)2 vitamin D deficiency. XLH manifests in early life with rickets and persists in adulthood with osseous and extraosseous manifestations. Conventional therapy (oral phosphate and calcitriol) improves some symptoms, but evidence show that it is not completely effective, and it can lead to nephrocalcinosis (NC) and hyperparathyroidism (HPT). Burosumab (anti-FGF23 antibody) has shown to be effective and safety in the clinical trials. METHODS: The current real-world collaborative study evaluated genetic, clinical and laboratory data of XLH Brazilian adult patients treated with burosumab. RESULTS: Nineteen unrelated patients were studied. Patients reported pain, limb deformities and claudication, before burosumab initiation. 78% of them were previously treated with conventional therapy. The severity of the disease was moderate to severe (15 patients with score >5). At the baseline, 3 patients presented NC (16.7%) and 12 HPT (63%). After 16 ± 8.4 months under burosumab, we observed a significant: increase in stature (p = 0.02), in serum phosphate from 1.90 ± 0.43 to 2.67 ± 0.52 mg/dL (p = 0.02); in TmP/GFR from 1.30 ± 0.46 to 2.27 ± 0.64 mg/dL (p = 0.0001), in 1,25 (OH)2 D from 50.5 ± 23.3 to 71.1 ± 19.1 pg/mL (p = 0.03), and a decrease in iPTH from 86.8 ± 37.4 pg/mL to 66.5 ± 31.1 (p = 0.002). Nineteen variants were found (10 novel). HPT tended to develop in patients with truncated PHEX variants (p = 0.06). CONCLUSIONS: This study confirms the efficacy and safety of burosumab on XLH adult patients observed in clinical trials. Additionally, we observed a decrease in iPTH levels in patients with moderate to severe HPT at the baseline.
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Anticorpos Monoclonais Humanizados , Raquitismo Hipofosfatêmico Familiar , Adulto , Humanos , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/genética , Anticorpos Monoclonais/uso terapêutico , Brasil , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Fosfatos/uso terapêuticoRESUMO
BACKGROUND: Patients with chronic kidney disease (CKD) have reduced expression of erythroid nuclear factor-related factor 2 (NRF2) and increased nuclear factor κB (NF-κB). "Food as medicine" has been proposed as an adjuvant therapeutic alternative in modulating these factors. No studies have investigated the effects of sulforaphane (SFN) in cruciferous vegetables on the expression of these genes in patients with CKD. OBJECTIVE: The study aimed to evaluate the effects of SFN on the expression of NRF2 and NF-κB in patients on hemodialysis (HD). DESIGN AND METHODS: A randomized, double-blind, crossover study was performed on 30 patients on regular HD. Fourteen patients were randomly allocated to the intervention group (1 sachet/day of 2.5 g containing 1% SFN extract with 0.5% myrosinase) and 16 patients to the placebo group (1 sachet/day of 2.5 g containing corn starch colored with chlorophyll) for 2 months. After a washout period of 2 months, the groups were switched. NRF2 and NF-κB mRNA expression was evaluated by real-time quantitative polymerase chain reaction, and tumor necrosis factor alpha and interleukin-6 levels were quantified by enzyme-linked immunosorbent assay. Malondialdehyde was evaluated as a marker of lipid peroxidation. RESULTS: Twenty-five patients (17 women, 55 [interquartile range = 19] years and 55 [interquartile range = 74] months on HD) completed the study. There was no significant difference concerning the expression of mRNA NRF2 (P = .915) and mRNA NF-κB (P = .806) after supplementation with SFN. There was no difference in pro-inflammatory and oxidative stress biomarkers. CONCLUSION: 150 µmol of SFN for 2 months had no antioxidant and anti-inflammatory effect in patients with CKD undergoing HD.
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Isotiocianatos , NF-kappa B , Insuficiência Renal Crônica , Sulfóxidos , Humanos , Feminino , NF-kappa B/genética , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estudos Cross-Over , Estresse Oxidativo , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etiologia , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , Suplementos NutricionaisRESUMO
BACKGROUND: Magnesium (Mg2+) is a fundamental mineral that maintains cellular function, and low levels may be linked to inflammation in patients with chronic kidney disease (CKD). This cross-sectional study evaluated the correlation between serum Mg2+ levels and the inflammatory status in patients undergoing dialysis. METHODS: Two hundred patients with CKD [150 undergoing hemodialysis (HD), 50 (18) years; BMI 24 (4.8) kg/m²; and 50 patients on peritoneal dialysis (PD), 54 (17.7) years; BMI, 27.5 (7.3) kg/m²] were included. Serum Mg2+ levels were evaluated using a colourimetric test and commercial kit. Inflammatory markers were assessed by ELISA and multiplex bead-based assay. Lipid peroxidation was evaluated using thiobarbituric acid-reactive substances. RESULTS: The median serum Mg2+ levels were 2.3 (0.5) mg/dL, and 21% of patients presented Mg2+ deficiency (< 2.07 mg/dL or 0.85 mmol/L). We found no difference in Mg2+ serum levels between the two groups. A significant negative correlation was observed between serum Mg2+ levels and plasma hs-CRP (r =-0.17, p = 0.01), IL-8 (r =-0.35, p = 0.01), and MCP-1 (r =-0.31, p = 0.03) levels. CONCLUSION: Mg2+ serum levels were negatively correlated with inflammatory status in patients with CKD on dialysis.
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Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Magnésio , Estudos Transversais , Inflamação , Insuficiência Renal Crônica/terapia , Diálise Renal , Proteína C-Reativa/análiseRESUMO
Abstract Introduction Turner syndrome (TS) affects ~ 1 in 2,500 live births. The presence of hearing alterations is one of the comorbidities found in this syndrome. Objective The present study aimed to evaluate the central auditory abilities in TS and to associate the alterations found with the cytogenetic pattern of the syndrome. Methods We included children and adults aged 9 to 39 years old, diagnosed with TS, with numerical or structural alterations of sex chromosomes in their karyotype. A battery of behavioral tests of central auditory processing (CAP) was performed, including a test within the modalities: monoaural low-redundancy, dichotic listening, binaural interaction, and temporal processing (resolution and ordering). We studied auditory skills in the total sample and in the sample stratified by age, divided into groups: G1 (9 to 13 years old), G2 (14 to 19 years old), and G3 (20 to 31 years old). For the association of the cytogenetic pattern, the division was T1 (chromosome monosomy X), and T2 (other TS cytogenetic patterns). Statistical analysis presented data expressed as median and interquartile range for numerical data and as frequency and percentage for categorical data. Results We found alterations in four auditory skills in the three age groups, but there was a statistically significant difference between the age groups only in the Gaps in Noise Test (GIN) (p-value = 0.009). Regarding karyotype, a greater number of alterations in the T1 cytogenetic pattern (chromosome monosomy X) was observed in four auditory skills, but without a statistically significant difference. Conclusion The alterations found point to an impairment in CAP in TS.
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Chronic kidney disease is a significant risk factor for cardiovascular disease. In addition to traditional risk factors, such as hypertension, dyslipidemia, diabetes and smoking, patients with chronic kidney disease have a uremic phenotype marked by premature aging, mitochondrial dysfunction, persistent low-grade inflammation, gut dysbiosis and oxidative stress. These complications contribute to abnormal vascular and myocardial remodeling processes, resulting in accelerated vascular calcification, cellular and organ senescence and a high risk of cardiovascular disease. Nonpharmacological strategies, such as increasing physical activity and a healthy diet, may slow the progression of kidney disease and consequently protect the heart. Thus, a deep promotion and advocacy of nutritional guidance based on scientific data is needed. This narrative review discusses how nutritional interventions may delay progressive organ damage in the kidney-heart axis.
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Doenças Cardiovasculares , Hipertensão , Insuficiência Renal Crônica , Humanos , Doenças Cardiovasculares/complicações , Rim , Insuficiência Renal Crônica/complicações , Fatores de RiscoRESUMO
Royal jelly (RJ) is a bee product produced by young adult worker bees, composed of water, proteins, carbohydrates and lipids, rich in bioactive components with therapeutic properties, such as free fatty acids, mainly 10-hydroxy-trans-2-decenoic acid (10-H2DA) and 10-hydroxydecanoic acid (10-HDA), and major royal jelly proteins (MRJPs), as well as flavonoids, most flavones and flavonols, hormones, vitamins and minerals. In vitro, non-clinical and clinical studies have confirmed its vital role as an antioxidant and anti-inflammatory. This narrative review discusses the possible effects of royal jelly on preventing common complications of non-communicable diseases (NCDs), such as inflammation, oxidative stress and intestinal dysbiosis, from the viewpoint of predictive, preventive and personalised medicine (PPPM/3PM). It is concluded that RJ, predictively, can be used as a non-pharmacological therapy to prevent and mitigate complications related to NCDs, and the treatment must be personalised.
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Atopic dermatitis (AD) is a chronic, relapsing, multifactorial inflammatory disease with genetic, environmental, and immunological characteristics. The quality of life and sleep of patients and their families are affected by AD, which triggers stress, described as one of the factors that worsens AD. Salivary biomarkers such as cortisol, alpha-amylase, chromogranin A, and melatonin have been associated with stress and sleep disturbances. Therefore, the evaluation of stress and sleep disorders using salivary biomarkers in AD patients is important. This review aims to describe the possible relationship between atopic dermatitis and stress, sleep disorders, and salivary biomarkers, seeking to contribute to better understanding and clinical management of AD. This descriptive study is characterized as a narrative literature review. A literature search was conducted of studies published in English and Portuguese between January 2012 and October 2022 that are available in electronic media from various databases, such as Scientific Electronic Library Online, Latin American and Caribbean Literature on Health Sciences, and PubMed. AD is associated with different degrees of impact on the lives of individuals who present with the disease. Psychological stress may induce changes in saliva composition and worsen AD; at the same time, the severity of the disease may be associated with emotional impact. Further studies are needed to assess and correlate AD severity, stress, and sleep disturbances with salivary biomarkers in order to better understand this association.
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INTRODUCTION: BTB and CNC homology 1 (Bach1) is a protein that antagonizes some actions of nuclear factor erythroid 2-related factor-2 (Nrf2), the master regulator of cytoprotective responses. Bach1 binds to genomic DNA and inhibits the synthesis of antioxidant enzymes, thereby increasing inflammation. Bach1 may be a therapeutic target for mitigating inflammation in chronic kidney disease (CKD) patients. However, no clinical study has been reported on Bach1 in this population. This study aimed to evaluate Bach1 mRNA expression with different treatments for CKD, including conservative treatment (nondialysis), hemodialysis (HD), and peritoneal dialysis (PD). METHODS: Twenty patients undergoing HD (56.5 [19] years), 15 on PD (54 [24] years) and 13 nondialysis patients (63 [10] years, with an estimated glomerular filtration rate of 41 [14] mL/min/1.73 m2 ) were enrolled in the study. The mRNA expression of Nrf2, NF-kB, heme oxygenase 1 (HO-1), and Bach1 was evaluated in peripheral blood mononuclear cells using quantitative real-time polymerase chain reaction. Malondialdehyde (MDA) was evaluated as a lipid peroxidation marker. Routine biochemical parameters were also evaluated. FINDINGS: As expected, patients on dialysis were more inflamed. Bach1 mRNA expression was significantly higher in patients undergoing HD than in PD and nondialysis patients (p < 0.007). The mRNA expression of HO-1, NF-kB, and Nrf2 was not different in the groups. CONCLUSION: In conclusion, CKD patients on HD exhibited an upregulation of Bach1 mRNA expression compared to patients on PD treatment and nondialysis CKD patients. The association between Nrf2 and Bach1 expression in these patients warrants further investigation.
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Fator 2 Relacionado a NF-E2 , Insuficiência Renal Crônica , Humanos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , NF-kappa B/metabolismo , Leucócitos Mononucleares/metabolismo , Diálise Renal , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/terapia , Inflamação , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Metabolic myopathies are a diverse group of rare genetic disorders associated with recurrent episodes of rhabdomyolysis, induced by triggers such as fever or exercise. In these disorders, the energetic metabolism is compromised resulting in damage of the muscle cells. The diagnosis can be challenging but is essential for the correct treatment. Carnitine palmitoytransferase II (CPT-II) deficiency is the most common long-chain fatty acid oxidation defect, with the adulthood form requiring additional external triggers. The authors present a case of a young-male adult with recurrent episodes of rhabdomyolysis, one of them presented with acute renal failure and acute hepatitis. The diagnostic is demanding, which requires a high level of suspicion. The adequate treatment of these patients improves the muscle function and prevents other episodes of severe rhabdomyolysis.
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BACKGROUND: Chronic kidney disease (CKD) patients on dialysis display a low-grade systemic inflammatory burden. Nutritional interventions designed to activate the cytoprotective nuclear factor erythroid-2-related factor 2 (Nrf2) and inhibit nuclear factor-kB (NF-κB) have been proposed to mitigate this burden. Several bioactive compounds have been investigated to achieve this, including propolis, a resin produced by Apis mellifera bees. Considering the safety and efficacy of propolis, it could be a strategy to benefit these patients. Still, there are no studies using propolis in patients with CKD on peritoneal dialysis (DP), and clinical studies to support this application are lacking. HYPOTHESIS/PURPOSE: The objective and novelty of the present study are to evaluate the effects of propolis supplementation on inflammatory markers in patients with CKD on PD. STUDY DESIGN: A longitudinal, double-blind, placebo-controlled trial with CKD patients on PD. METHODS: The patients were randomised into two groups: propolis that received four capsules of 100 mg (400 mg/day), containing concentrated and standardised dry EPP-AF® Brazilian green propolis extract) or placebo, four capsules of 100 mg (400 mg/day), of magnesium stearate, silicon dioxide, and microcrystalline cellulose, for two months. Plasma levels of inflammatory cytokines, including tumour necrosis factor (TNF-α) and interleukin-6 (IL-6), were evaluated by ELISA. Quantitative real-time PCR analyses were performed to evaluate the transcriptional expression levels of Nrf2 and NF-κB in peripheral blood mononuclear cells (PBMCs). Plasma malondialdehyde (MDA) levels, a lipid peroxidation marker, was measured as thiobarbituric acid reactive substances (TBARS). Routine biochemical markers, including C-reactive protein (CRP), were analysed using commercial kits. Carotid Intima-Media Thickness (CIMT) was measured with a doppler ultrasonography device. The study was registered on ClinicalTrials.gov under the number NCT04411758. RESULTS: A total of 19 patients completed the study, ten patients in the propolis group (54 ± 1.0 years, five men, 7.2 (5.1) months on PD) and 9 in the placebo group (47.5 ± 15.2 years, three men, 10.8 (24.3) months on PD). The plasma levels of TNF-α reduced significantly (p = 0.02), and expression of Nrf2 showed a trend to increase (p = 0.07) after propolis supplementation. CONCLUSION: EPP-AF® Green Propolis extract (400 mg/day) supplementation for two months appears as a potential strategy to mitigate inflammation, reducing TNF-α plasma levels in CKD patients on PD.
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Diálise Peritoneal , Própole , Insuficiência Renal Crônica , Animais , Biomarcadores , Brasil , Espessura Intima-Media Carotídea , Método Duplo-Cego , Inflamação/tratamento farmacológico , Leucócitos Mononucleares/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Fator de Necrose Tumoral alfa , HumanosRESUMO
BACKGROUND: Inflammation and oxidative stress lead to a high risk of cardiovascular disease in patients with chronic kidney disease (CKD). Food rich in polyphenols such as dark chocolate may be an effective strategy to mitigate inflammation and delay CKD complications, outwith sensorial pleasure promotion. The aim of this study was to evaluate the effects of dark chocolate on inflammation and oxidative stress markers in patients with CKD on hemodialysis (HD). METHODS: A clinical trial was carried out with 59 patients who were allocated into the chocolate group [40g of dark chocolate (70% cocoa) offered during HD sessions, 3×/week] or the control group with any intervention for two months. Plasma levels of the inflammatory cytokines TNF-α and IL-6 were evaluated by the ELISA method. Thiobarbituric acid reactive substances such as malondialdehyde (MDA) and LDLox levels were evaluated as lipid peroxidation markers. Routine biochemical parameters were analysed using commercial BioClin® kits. RESULTS: Thirty-five patients completed the chocolate group (18 men, 53.0 (16) years and 31.0 (39) months on HD) and 11 in the control group (7 men, 48.0 (17.5) years and 44.0 (56.5) months on HD). Regarding the differences between the groups, the patients who received dark chocolate had reduced plasma levels of TNF-α compared to the control (p = 0.008). No significant changes were observed in the oxidative stress parameters evaluated in both groups. Routine biochemical (including phosphorus and potassium levels) and anthropometric parameters and food intake were not changed after the study period. CONCLUSION: The intervention with dark chocolate (70% cocoa) for two months reduced the plasma levels of TNF-α in patients with CKD on HD. In addition, it is essential to emphasise that chocolate intake did not increase the plasma levels of phosphorus and potassium in these patients. This study was registered at clinicaltrials.gov as NCT04600258.
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Chocolate , Diálise Renal , Insuficiência Renal Crônica , Fator de Necrose Tumoral alfa , Humanos , Masculino , Cacau , Inflamação , Fator de Necrose Tumoral alfa/sangue , Feminino , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Down syndrome is the main genetic cause of intellectual disability. Many studies describe the clinical characteristics of DS patients; however, few have investigated the clinical profile of mothers who have children with DS. Advanced maternal age (≥ 35 years old) is a risk factor for DS. Although there is an overall increase in pregnancies among women with advanced maternal age, there is still a lack of awareness of the increased risk of aneuploidy. Here, we reported the clinical and epidemiological profile of DS children and their mothers in a public reference hospital in the State of Rio de Janeiro, Brazil. For data collection, we performed a face-to-face interview guided by a structured questionnaire with closed-ended questions. A total of 344 individuals, 172 mothers and their DS children, were included in this study. Our results show that 56% of the mothers sampled were ≥ 35 years of age at childbirth. Although 98% of them received prenatal care, only 4% obtained a prenatal diagnosis of DS. Most mothers reported not drinking alcohol or smoking cigarettes during pregnancy. Furthermore, 91% of women took prenatal vitamins and supplements; however, 47% were not aware of their benefits for a healthy pregnancy. Given the strict correlation between advanced maternal age and DS, prenatal care should include genetic counseling for women over 35 years of age. This study highlights the importance of prenatal care and the urgent need for better DS screening allowing for immediate postnatal care, positively impacting the life expectancy of these patients.
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Abstract Mucopolysaccharidosis type II (MPS II) is a rare genetic, multiorgan disease. Little information about the Brazilian context is available to date; thus, this descriptive subgroup analysis was conducted on Brazilian data from the Hunter Outcome Survey (HOS), including clinical characteristics among MPS II patients from Brazil. HOS is a global, multi-center, long-term, observational registry of patients with MPS II (NCT03292887). Variables related to organ system involvement, signs and symptoms, surgical procedures and survival among Brazilian patients were extracted from HOS database. Data from 153 Brazilian patients with MPS II were analyzed. Musculoskeletal (96.6%), abdomen/gastrointestinal (95.2%), neurological (88.7%), pulmonary (86.2%), and ear (81.3%) were the most frequently observed organ/systems involved. Regarding signs and symptoms, the most prevalent symptom was coarse facial features consistent with the disease (94.6%), followed by joint stiffness and limited function (89.3%), hernia (84.2%) and hepatomegaly (82.2%). Median survival time was 22.0 years, and the major cause of death was respiratory failure (31.8%). These data may be helpful to understand disease characteristics and to help improve the quality of MPS II patient care in Brazil.