Higher urea-to-albumin ratio is associated with mortality risk in critically ill COVID-19 patients.

BACKGROUND: This study aimed to evaluate the ability of the urea-to-albumin ratio (UAR) to predict mortality in critically ill coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study included adult patients admitted with COVID-19 at two intensive care units (ICUs) at the University Hospital. Serum urea and albumin concentrations at ICU admission were used to calculate the UAR. All patients were followed up during hospitalization, and the ICU mortality rate was recorded. RESULTS: Two hundred and eleven patients were evaluated. The mean age was 57.8 ± 15.5 years, and 54% were male. Approximately 84.4% of patients were considered to be at nutritional risk by the NRS 2002, and the median UAR was 18.3 (10.5-34.8). The length of stay in the ICU was 10 (6-16) days, 38.4% of the patients required dialysis, and 64.9% died. Age, male sex, need of hemodialysis, lactate level, and inflammatory parameters were associated with higher mortality. Patients non-survivors had a higher UAR (23.7 [13.6-41.8] vs. 10.9 [8.5-16.8]; p < 0.001). The cutoff point with the best performance of UAR in the ROC curve for predicting mortality was ≥12.17 (AUC: 0.7201; CI 95%: 0.656-0.784). Additionally, the risk of mortality was 2.00-fold in the group of patients with UAR ≥12.17 (HR: 2.00 CI: 1.274-3.149; p = 0.003) and remained significant after adjusted analyzes (models 1 and 2). CONCLUSION: Our data suggest that a UAR ≥12.17 increased the risk of mortality by 2.00-fold in critically ill COVID-19 patients.

Beans comsumption can contribute to the prevention of cardiovascular disease.

Cardiovascular diseases (CVD) are the major cause of global mortality, accounting for 31% of deaths worldwide. Healthy eating habits based on the consumption of bioactive molecules present in plant-based diets can contribute to the prevention of CVD. In this context, the consumption of common beans (Phaseolus vulgaris L.) is relevant. There are several species of beans, all of which provide proteins, carbohydrates, dietary fiber, vitamins, minerals, and phenolic compounds. More recently, the complexity of phytochemical components has expanded, including the role of antinutritional factors in nutrient bioavailability and immune responses. Experimental and clinical studies have shown that the consumption of beans results in less food consumption, control of body weight, and improvement of metabolic biochemical parameters. Thus, the consumption of beans is associated with a decrease in CVD risk factors. To date, there have been no interventional studies assessing CVD outcomes, such as hospitalization, infarction, and mortality, in the context of bean consumption. Furthermore, studies on the effect of bean consumption on metabolomics and intestinal microbiota are lacking. The purpose of this review is to explore the nutritional properties of beans and discuss the main effects of the consumption of beans on cardiovascular health. In conclusion, eating habits based on the consumption of bioactive molecules present in beans can contribute to the prevention of cardiovascular disease. Furthermore, there is a large gap in the literature regarding the consumption of beans associated with clinical outcomes, such as hospitalization and mortality.

Circulating miRNAs are associated with frailty and ST-elevation myocardial infarction pathways.

BACKGROUND: Frailty and ST-Elevation Myocardial Infarction (STEMI) share similar molecular pathways. Specific biomarkers, such as microRNAs (miRNAs), may provide insights into the molecular mechanisms that cause the relationship between frailty and STEMI. OBJECTIVE: Our aim was to identify and compare circulating miRNA levels between frail and non-frail older adults following STEMI and comprehend the regulatory miRNA-gene networks and pathways involved in this condition. METHODS: This exploratory study is a subanalysis of a larger observational study. In this study, we selected patients ≥ 65 years old, following STEMI, with pre-frail/frail (n=5) and non-frail (n=4) phenotype evaluated using the Clinical Frailty Scale and serum circulating miRNA levels were analyzed. RESULTS: Pre-frail/frail patients had greater serum levels of 53 miRNAs, compared with non-frail patients. Notably, miR-103a-3p, miR-598-3p, and miR-130a-3p were the top three significantly deregulated miRNAs predicted to modulate gene expression associated with aging. Additional computational analyses showed 7,420 predicted miRNA gene targets, which were regulated by at least two of the 53 identified miRNAs. Pathway enrichment analysis showed that axon guidance and MAPK signaling were among pathways regulated by miRNA target genes. CONCLUSIONS: These novel findings suggest a correlation between the identified miRNAs, target genes, and pathways in pre-frail and frail patients with myocardial infarction.

Comparison between FRAIL Scale and Clinical Frailty Scale in predicting hospitalization in hemodialysis patients.

BACKGROUND: To assess the prevalence of frailty by the Clinical Frailty Scale (CFS) and the 5-item FRAIL scale and their association with hospitalization in hemodialysis (HD) patients. METHODS: This was a prospective observational study. We included patients of both genders ≥ 18 years old in HD treatment for at least 3 months. Demographic, clinical, and routine laboratory data were retrieved from the medical charts. Two different frailty assessment tools were used, the CFS and the FRAIL scale. Participants were followed up for 9 months and hospitalizations for all causes were evaluated. A Venn diagram was constructed to show the overlap of possible frailty and pre-frailty. Cox regression was used to identify the association between frailty and hospitalization. The significance level was 5%. RESULTS: A total of 137 subjects were included in the analysis. The median age was 61 (52-67) years and 60% were male. The hospitalization rate and mortality in 9 months were 22.6% and 7.29%, respectively. Regarding frailty, the overall prevalence was 13.8% assessed by CFS and 36.5% according to the FRAIL scale. In the Cox regression, frailty by FRAIL scale was associated with a 2.8-fold increase in the risk of hospitalization (OR = 2.880; 95% CI = 1.361-6.096; p = 0.006), but frailty assessed by the CFS was not associated with the need for hospitalization. CONCLUSION: In HD patients, the FRAIL scale proved to be an easy-to-apply tool, identifying a high prevalence of frailty and being a predictor of hospital admission.

Influence of the type of electrodes in the assessment of body composition by bioelectrical impedance analysis in the supine position.

BACKGROUND & AIMS: The main source of error in body composition assessment of bedridden patients by bioelectrical impedance analysis (BIA) is the electrode inadequacy and placement. As electrocardiogram (ECG) electrodes are often used for BIA measurements, this study aimed to compare three of them with a reference BIA electrode. METHODS: BIA was performed sequentially on 24 healthy subjects in the supine position, using 3 different ECG electrodes (3M® Red Dot® 2330; Ambu® BlueSensor 2300; Ambu® BlueSensor SU-00-C) and the reference electrode (Bianostic AT®) for the BIA device (Nutriguard-M®, Data Input, Germany). Resistance (R), reactance (Xc), phase angle (PhA), appendicular skeletal muscle index (ASMI), fat-free mass index (FFMI) and fat mass percentage (FM%) obtained with the different electrodes were compared using Bland-Altman plots, repeated measures one-way ANOVA and paired t-test. Patient characteristics potentially involved in BIA measurement differences were assessed using linear regression analysis. RESULTS: The study population consisted of 9 men and 15 women, 33% and 47% of whom were overweight, respectively. The measured R was within the physiological range for all men (428-561 Ω) and women (472-678 Ω), regardless of the type of electrodes used. Compared to the reference electrode, the 3M® Red Dot® 2330 and Ambu® BlueSensor SU-00-C electrodes gave significantly different Xc and PhA values, but only the Ambu® BlueSensor SU-00-C gave significantly different ASMI, FFMI and FM% at 50 kHz, with biases of -0.2 kg/m2, -0.3 kg/m2 and +1.4%, respectively. The higher the current frequency, the lower was the Xc and PhA measured by the Ambu® BlueSensor SU-00-C compared to the reference electrode. These measurement differences seemed mainly due to the too small gel area of the Ambu® BlueSensor SU-00-C (154 mm2) compared to the reference electrode (1311 mm2). CONCLUSIONS: The use of electrodes with small gel area affects BIA measurement in the supine position, especially when PhA is used as an indicator of the nutritional status. Therefore, it is essential to specify the type of electrodes and carry out comparative tests before changing consumables for body composition assessment, to ensure BIA measurement reliability in clinical and research settings.

Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats.

AIM: Evaluate the influence of doxycycline, an anti-inflammatory and matrix metalloproteinase (MMP) inhibitor, on the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. METHODS: We allocated male Wistar rats into four groups: control (C), doxorubicin (D), doxycycline (inhibitor of MMP, IM), and Dox + doxycycline (DIM). Groups IM and DIM received doxycycline (5 mg/kg, IP) once a week for 4 weeks. In addition, 48 h after every doxycycline injection, groups D and DIM received Dox (5 mg/kg, IP). We performed echocardiogram and evaluated TIMP-4 and collagen I protein expression, MMP-2 activity, and oxidative stress and myocardial metabolism. RESULTS: Doxorubicin promotes left atrium (LA) and left ventricle (LV) dilatation and decreases in LV fractional shortening, which was improved by doxycycline. Moreover, doxycycline attenuated the LV cardiomyocyte hypertrophy and collagen type I expression. Doxorubicin increased phosphofructokinase and decreased beta-hydroxyacyl Co-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, and ATP synthase activity, which was partially attenuated by doxycycline. Lastly, doxycycline improved antioxidant enzyme activity in the DIM group. CONCLUSION: Doxorubicin increases oxidative stress and promotes changes in myocardial energy metabolism, accompanied by structural and functional changes. Doxycycline attenuated the doxorubicin-induced cardiotoxicity, at least in part, through changes in myocardial energy metabolism.

Association between frailty and C-terminal agrin fragment with 3-month mortality following ST-elevation myocardial infarction.

The objective of this study was to evaluate the association between frailty, evaluated by the Clinical Frailty Scale (CFS) and FRAIL scale, and C-terminal agrin fragment (CAF) levels with 3-month mortality following ST-segment elevation myocardial infarction (STEMI). This was a prospective observational study that included patients over the age of 18 years with STEMI admitted to the coronary intensive care unit. Within 48 h of admission, the CFS and FRAIL scale were applied and blood samples collected for serum CAF evaluation. Patients were followed for 3 months after hospital discharge, and mortality was recorded. One hundred and eleven patients were included; mean age was 62.3 ±â€¯12.4 years, 61.3% were male and 11.7% died during the 3 months of follow-up. According to the CFS, 79.3% of the patients were classified as not frail, 12.6% as pre-frail and 8.1% as frail. According to the FRAIL scale, 31.5% of the patients were classified as not frail, 53.2% as pre-frail and 15.3% as frail. In univariate analysis, the CFS but not FRAIL scale was associated with mortality. In multiple logistic regression analysis, pre-frail/frail according to CFS (odds ratio [OR]: 6.118; CI 95%: 1.344-27.848; p = 0.019) and CAF levels (OR: 0.943; CI 95%: 0.896-0.992; p = 0.024) were associated with increased 3-month mortality. In a sub-analysis of 53 patients ≥65 years, CFS and CAF levels were associated with 3-month mortality. In conclusion, CAF levels and frailty determined by the CFS were associated with 3-month mortality after STEMI in the general and older population.

"Sapatão" é só para os íntimos: vínculo no cuidado de mulheres lésbicas e bissexuais / "Tortillera" es solo para los íntimos: vínculo en el cuidado de mujeres lesbianas y bisexuales / "Sapatão" is only for the intimate: link in the care of lesbian and bisexual women

Mulheres lésbicas e bissexuais enfrentam dificuldades para o reconhecimento de suas necessidades de saúde, resultando em iniquidades. O objetivo deste estudo foi compreender a construção de vínculo no cuidado à saúde de lésbicas e bissexuais. Adotou-se metodologia qualitativa, utilizando-se entrevistas semiestruturadas presenciais e on-line. A população foi composta por 14 mulheres, residentes em São Paulo, SP, Brasil. Para a análise de conteúdo, foram considerados os marcadores sociais da diferença e a relação das entrevistadas com movimentos sociais. Evidenciou-se que a articulação de marcadores sociais da diferença pode contribuir com a potencialização da exclusão e que a participação em movimentos sociais projeta as mulheres mais ativamente na reivindicação de seu cuidado. Esses dois componentes são atravessadores importantes na construção de vínculo.(AU)

Las mujeres lesbianas y bisexuales enfrentan dificultades para el reconocimiento de sus necesidades de salud, resultando en iniquidades. El objetivo de este estudio fue comprender la construcción de un vínculo en el cuidado de la salud de lesbianas y bisexuales. Se adoptó la metodología cualitativa, utilizándose entrevistas semiestructuradas presenciales y online. La población fue formada por 14 mujeres, residentes en São Paulo (SP) Brasil. Para el análisis, realizado por medio del análisis de contenido, se consideraron los marcadores sociales de la diferencia y la relación de las entrevistadas con movimientos sociales. Se puso en evidencia que la articulación de marcadores sociales de la diferencia puede contribuir para potencializar la exclusión y que la participación en movimientos sociales proyecta a las mujeres más activamente en la reivindicación de su cuidado. Esos dos componentes son factores atravesadores importantes en la construcción de vínculo.(AU)

Lesbian and bisexual women face difficulties in having their health needs recognized resulting in inequities. The objective of this study was to understand the creation of bonds in the health care for lesbians and bisexuals. A qualitative methodology was adopted, using face-to-face and online semi-structured interviews. The population consisted of 14 women, living in São Paulo (SP), Brazil. For the analysis, carried out through content analysis, the social markers of difference and the interviewees' relationship with social movements were considered. It was evidenced that the articulation of social markers of difference can contribute to the potentiation of exclusion and that participation in social movements projects women more actively in claiming their care. These two components are important intermediaries in bond creation.(AU)

Meal timing and frequency implications in the development and prognosis of chronic kidney disease.

Patients with chronic kidney disease (CKD) have a higher risk of death than the general population, the main cause being cardiovascular disease (CVD). Nutrition plays a key role in the prevention and treatment of CVD and kidney diseases. Currently, new evidence reinforces the importance of specific foods and general dietary patterns rather than isolated nutrients for cardiovascular risk. In addition, dietary patterns and healthy eating habits seem extremely relevant in decreasing risk factors. Epidemiologic and clinical intervention studies have suggested that late-night dinner and skipping breakfast are associated with an increased risk of obesity, insulin resistance, and CVD. In CKD, despite important changes in nutritional counseling in recent decades, less attention has been paid to meal timing and frequency. Therefore, the purpose of this review is to discuss the evidence of meal timing and frequency in CKD development and prognosis, presented under three main topics: risk of developing CKD, importance of dietary habits, and implications of fasting.

Pera orange (Citrus sinensis) and Moro orange (Citrus sinensis (L.) Osbeck) juices attenuate left ventricular dysfunction and oxidative stress and improve myocardial energy metabolism in acute doxorubicin-induced cardiotoxicity in rats.

OBJECTIVES: Doxorubicin is a highly effective chemotherapeutic agent for treating several types of cancer; however, it can induce cardiotoxicity. We evaluated the influence of Pera and Moro orange juices on cardiac remodeling induced by acute administration of doxorubicin in rats. METHODS: We allocated 120 male Wistar rats into six groups: control (C), Pera orange juice (PO), Moro orange juice (MO), doxorubicin (D), doxorubicin + Pera orange juice (DPO), and doxorubicin + Moro orange juice (DMO). Groups PO and DPO received Pera orange juice, MO and DMO received Moro orange juice, and C and D received water with maltodextrin (100 g/L) for 4 wk. Subsequently, groups D, DPO, and DMO received 20 mg/kg doxorubicin and C, PO, and MO received saline. Echocardiogram and euthanasia were performed 48 h after doxorubicin injection. Juice and animal-serum flavonoid identification and quantification were evaluated by liquid chromatography/electrospray ionization multistage mass spectrometry. Oxidative stress and myocardial metabolism were evaluated by spectrophotometry. RESULTS: Systolic and diastolic left ventricular dysfunction increased oxidative stress and pathologic changes in myocardial energy metabolism of rats treated with doxorubicin. Intake of both orange juices improved left ventricular function, decreased oxidative stress, and attenuated the myocardial energy metabolism changes. Moro orange juice had a more pronounced effect than Pera orange juice in glutathione peroxidase activity, citrate synthase, and ß-hydroxyacyl-CoA dehydrogenase activity. CONCLUSIONS: Pera and Moro orange juices attenuated cardiac remodeling induced by doxorubicin, improved myocardial energy metabolism, and attenuated oxidative stress. However, Moro orange juice was more effective than Pera orange juice in modifying energy metabolism.

Urea to albumin ratio is a predictor of mortality in patients with septic shock.

BACKGROUND: The purpose of this study was to evaluate urea to albumin ratio (UAR) as predictor of mortality in patients with septic shock. METHODS: We included all individuals aged ≥ 18 years, with the diagnosis of septic shock at Intensive Care Unit (ICU) admission. Laboratorial and clinical data was recorded within the first 24 h of the patient's admission. Serum urea and albumin concentration were used for UAR calculation. All patients were followed during their ICU stay and the mortality rate was recorded. RESULTS: 222 patients were included in the analysis; the mean age was 62.3 ± 15.1 years and 66% were male. Mortality rate during the ICU stay was 59.9% and the median UAR was 40.7 (24.5-66.1). The UAR was also higher in patients who died in the ICU and was positively correlated with APACHE II, SOFA score and CRP. The ROC ICU mortality development (AUC: 0.617; CI 95%: 0.541-0.693; p: 0.003) at the cutoff of ≥47.25. Furthermore, UAR values were associated with ICU mortality when adjusted by age, sex and APACHE II (OR: 1.011; CI95%:1.000-1.022; p = 0.043) and when adjusted by lactate (OR: 1.014; CI95%:1.003-1.024; p = 0.009). CONCLUSIONS: Our data suggest that UAR could play a role as predictor of ICU mortality in patients with septic shock.

Insights Into Thiamine Supplementation in Patients With Septic Shock.

Septic shock is associated with unacceptably high mortality rates, mainly in developing countries. New adjunctive therapies have been explored to reduce global mortality related to sepsis. Considering that metabolic changes, mitochondrial dysfunction and increased oxidative stress are specific disorders within the path of septic shock, several micronutrients that could act in cellular homeostasis have been studied in recent decades. Thiamine, also known as vitamin B1, plays critical roles in several biological processes, including the metabolism of glucose, synthesis of nucleic acids and reduction of oxidative stress. Thiamine deficiency could affect up to 70% of critically ill patients, and thiamine supplementation appears to increase lactate clearance and decrease the vasopressor dose. However, there is no evident improvement in the survival of septic patients. Other micronutrients such as vitamin C and D, selenium and zinc have been tested in the same context but have not been shown to improve the outcomes of these patients. Some problems related to the neutrality of these clinical trials are the study design, doses, route, timing, length of intervention and the choice of endpoints. Recently, the concept that multi-micronutrient administration may be better than single-micronutrient administration has gained strength. In general, clinical trials consider the administration of a single micronutrient as a drug. However, the antioxidant defense is a complex system of endogenous agents in which micronutrients act as cofactors, and the physiological interactions between micronutrients are little discussed. In this context, the association of thiamine, vitamin C and corticoids was tested as an adjunctive therapy in septic shock resulting in a significant decrease in mortality. However, after these initial results, no other study conducted with this combination could reproduce those benefits. In addition, the use of low-dose corticosteroids is recommended in patients with septic shock who do not respond to vasopressors, which can affect the action of thiamine. Therefore, given the excellent safety profile, good biologic rationale and promising clinical studies, this review aims to discuss the mechanisms behind and the evidence for single or combined thiamine supplementation improving the prognosis of patients with septic shock.

Evaluation of peptidylarginine deiminase 4 and PADI4 polymorphisms in sepsis-induced acute kidney injury.

BACKGROUND: The aim of this study is to evaluate the peptidylarginine deiminase 4 (PAD 4) concentration and PADI4 polymorphisms as predictors of acute kidney injury (AKI) development, the need for renal replacement therapy (RRT), and mortality in patients with septic shock. METHODS: We included all individuals aged ≥ 18 years, with a diagnosis of septic shock at ICU admission. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentration and its PADI4 polymorphism (rs11203367) and (rs874881). Patients were monitored during their ICU stay and the development of SAKI was evaluated. Among the patients in whom SAKI developed, mortality and the need for RRT were also evaluated. RESULTS: There were 99 patients, 51.5% of whom developed SAKI and of these, 21.5% needed RRT and 80% died in the ICU. There was no difference between PAD4 concentration (p = 0.116) and its polymorphisms rs11203367 (p = 0.910) and rs874881 (p = 0.769) in patients in whom SAKI did or did not develop. However, PAD4 had a positive correlation with plasma urea concentration (r = 0.269 and p = 0.007) and creatinine (r = 0.284 and p = 0.004). The PAD4 concentration and PADI4 polymorphisms were also not associated with RRT and with mortality in patients with SAKI. CONCLUSION: PAD4 concentration and its polymorphisms were not associated with SAKI development, the need for RRT, or mortality in patients with septic shock. However, PAD4 concentrations were associated with creatinine and urea levels in these patients.

Evaluation of peptidylarginine deiminase 4 and PADI4 polymorphisms in sepsis-induced acute kidney injury

SUMMARY BACKGROUND: The aim of this study is to evaluate the peptidylarginine deiminase 4 (PAD 4) concentration and PADI4 polymorphisms as predictors of acute kidney injury (AKI) development, the need for renal replacement therapy (RRT), and mortality in patients with septic shock. METHODS: We included all individuals aged ≥ 18 years, with a diagnosis of septic shock at ICU admission. Blood samples were taken within the first 24 hours of the patient's admission to determine serum PAD4 concentration and its PADI4 polymorphism (rs11203367) and (rs874881). Patients were monitored during their ICU stay and the development of SAKI was evaluated. Among the patients in whom SAKI developed, mortality and the need for RRT were also evaluated. RESULTS: There were 99 patients, 51.5% of whom developed SAKI and of these, 21.5% needed RRT and 80% died in the ICU. There was no difference between PAD4 concentration (p = 0.116) and its polymorphisms rs11203367 (p = 0.910) and rs874881 (p = 0.769) in patients in whom SAKI did or did not develop. However, PAD4 had a positive correlation with plasma urea concentration (r = 0.269 and p = 0.007) and creatinine (r = 0.284 and p = 0.004). The PAD4 concentration and PADI4 polymorphisms were also not associated with RRT and with mortality in patients with SAKI. CONCLUSION: PAD4 concentration and its polymorphisms were not associated with SAKI development, the need for RRT, or mortality in patients with septic shock. However, PAD4 concentrations were associated with creatinine and urea levels in these patients.

RESUMO OBJETIVO: Avaliar a concentração da peptidilarginina deiminase 4 (PAD4) e os polimorfismos de PADI4, como preditores de desenvolvimento de lesão renal aguda, necessidade de terapia renal substitutiva (TRS) e mortalidade em pacientes com choque séptico. MÉTODOS: Foram incluídos indivíduos com idade ≥18 anos, com diagnóstico de choque séptico na admissão na Unidade de Terapia Intensiva (UTI). Amostras de sangue foram coletadas nas primeiras 24 horas após a admissão do paciente para determinar a concentração sérica de PAD4 e seus polimorfismos PADI4 (rs11203367) e (rs874881). Os pacientes foram acompanhados durante a internação na UTI e tiveram avaliados desenvolvimento da lesão renal aguda séptica (Sepsis-induced acute kidney injury - Saki), necessidade TRS e mortalidade. RESULTADOS: Foram avaliados 99 pacientes; 51,5% desenvolveram Saki e, desses, 21,5% necessitaram de TRS e 80% morreram na UTI. Não houve diferença entre a concentração de PAD4 (p=0,116) e seus polimorfismos rs11203367 (p=0,910) e rs874881 (p=0,769) entre os pacientes. No entanto, o PAD4 apresentou correlação positiva com a concentração plasmática de ureia (r=0,269; p=0,007) e creatinina (r=0,284; p=0,004). A concentração de PAD4 e os polimorfismos da PADI4 também não foram associados à TRS e à mortalidade em pacientes com Saki. CONCLUSÕES: A concentração de PAD4 e seus polimorfismos não foram associados ao desenvolvimento de Saki, à necessidade de TRS ou à mortalidade em pacientes com choque séptico. No entanto, as concentrações de PAD4 foram associadas às concentrações de creatinina e ureia nesses pacientes.

Effects of fluoride on insulin signaling and bone metabolism in ovariectomized rats.

Fluoride is an essential trace element for the maintenance of bone health owing to its capacity to stimulate proliferation and osteoblastic activity that can lead to increased bone formation. However, excessive sodium fluoride (NaF) intake can impair carbohydrate metabolism thereby promoting hyperglycemia, insulin resistance, and changes in insulin signaling. Thus, this study aimed to evaluate the effect of chronic treatment with NaF in bone metabolism, insulin signaling, and plasma concentrations of glucose, insulin, tumor necrosis factor-α (TNF-α), osteocalcin (OCN), and fluoride in ovariectomized rats. Thirty-two ovariectomized Wistar rats were randomly distributed into two groups: Control (OVX-C) and those undergoing treatment with NaF (50mg F/L) in drinking water for 42days (OVX-F). Glucose and insulin levels were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). Akt serine phosphorylation was evaluated by western blotting. Plasma concentrations of TNF-α and OCN were evaluated by ELISA. The left and right tibia was collected for immunohistochemical and histomorphometric analysis, respectively. Chronic treatment with NaF promoted insulin resistance, decreased insulin signal, increased plasma concentration of insulin, fluoride, OCN and TNF-α, decreased trabecular bone area of the tibia, and caused changes in bone metabolism markers in ovariectomized rats. These results suggest the need for caution in the use of NaF for the treatment of osteoporosis, especially in postmenopausal woman.

Effect of Sodium Fluoride on Bone Biomechanical and Histomorphometric Parameters and on Insulin Signaling and Insulin Sensitivity in Ovariectomized Rats.

Osteoporosis is a systemic disease characterized by bone degradation and decreased bone mass that promotes increased bone fragility and eventual fracture risk. Studies have investigated the use of sodium fluoride (NaF) for the treatment of osteoporosis. However, fluoride can alter glucose homeostasis. The aim of this study was to evaluate the effects of NaF intake (50 mg/L) from water on the following parameters of ovariectomized (OVX) rats: (1) tyrosine phosphorylation status of insulin receptor substrate (pp185 (IRS-1/IRS-2)) in white adipose tissue; (2) insulin sensitivity; (3) plasma concentrations of glucose, insulin, total cholesterol, triglyceride, TNF-α, IL-6, osteocalcin, calcium, and fluoride; (4) bone density and biomechanical properties in the tibia; and (5) tibia histomorphometric analysis. Fifty-two Wistar rats (2 months old) were ovariectomized and distributed into two groups: control group (OVX-C) and NaF group (OVX-F), which was subjected to treatment with NaF (50 mg/L) administered in drinking water for 42 days. The chronic treatment with NaF promoted (1) a decrease in pp185 (IRS-1/IRS-2) tyrosine phosphorylation status after insulin infusion in white adipose tissue and in insulin sensitivity; (2) an increase in the plasma concentration of insulin, fluoride, osteocalcin, calcium, triglyceride, VLDL-cholesterol, TNF-α, and IL-6; (3) a reduction in the trabecular width, bone area, stiffness, maximum strength, and tenacity; (4) no changes in body weight, food and water intake, plasma glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, bone mineral content, and bone mineral density. It was concluded that chronic treatment with NaF (50 mg/L) in OVX rats causes a decrease in insulin sensitivity, insulin signaling transduction, and biochemical, biomechanical, and histomorphometric bone parameters.

Avaliação de marcadores ósseos e sinal insulínico em ratas ovariectomizadas tratadas com fluoreto de sódio / Evaluation of bone markers and insulin signalling in ovariectomized rats treated with sodium fluoride

O flúor é um elemento traço essencial para a manutenção da saúde óssea, devido à capacidade de estimular a proliferação osteoblástica, levando ao aumento da formação óssea. No entanto, a ingestão excessiva de fluoreto de sódio pode prejudicar o metabolismo dos carboidratos, promovendo hiperglicemia, resistência à insulina e alterações no sinal insulínico. Dessa forma, este estudo teve como objetivo avaliar o efeito do tratamento crônico com NaF no metabolismo ósseo, na sinalização insulínica e nas concentrações plasmáticas de glicose, insulina, flúor, TNF-α e osteocalcina em ratas ovariectomizadas. Trinta e seis ratas Wistar ovariectomizadas foram distribuídas aleatoriamente em dois grupos: OVX-C, como grupo controle, e grupo OVX-F, que foi submetido ao tratamento com NaF (50 mg F/L) na água de beber durante 42 dias. Foram determinadas as concentrações plasmáticas de glicose e insulina, seguido pelo cálculo do HOMA-IR. A fosforilação em serina da Akt foi avaliada pelo método de Western blotting. As tíbias direita e esquerda foram coletadas para análises imuno-histoquímica e histomorfométrica. Os resultados do presente estudo demonstraram que o tratamento crónico com NaF promoveu resistência à insulina, diminuição do sinal insulínico, aumento das concentrações plasmáticas de insulina, flúor, osteocalcina e TNF-α; diminuição da área óssea trabecular da tíbia e alterações nos marcadores do metabolismo ósseo em ratas ovariectomizadas. Esses resultados sugerem cautela no uso de NaF para o tratamento da osteoporose, especialmente em mulheres na pós-menopausa(AU)

Fluoride is an essential trace element for the maintenance of bone health due its capacity of stimulating the proliferation and osteoblastic activity that can lead to increase bone formation. However, excessive sodium fluoride intake can impair carbohydrate metabolism, promoting hyperglycemia, insulin resistance and change in insulin signal. Thus, this study aimed to evaluate the effect of chronic treatment with NaF in bone metabolism; insulin signaling; plasma concentrations of glucose, insulin, TNF-α, osteocalcin and fluoride in ovariectomized rats. Thirty six ovariectomized Wistar rats were randomly distributed into two groups: OVXC, as control group, and OVX-F group, undergoing treatment with NaF (50mg F/L) in drinking water for 42 days. Plasma concentration of glucose and insulin were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). The Akt serine phosphorylation was evaluated by western blotting. The right and left tibias were collected for immunohistochemical and histomorphometric analysis, respectively. The chronic treatment with NaF promoted insulin resistance; decreased insulin signal; increase in the plasma concentration of insulin, fluoride, osteocalcin and TNF-α; decreased trabecular bone area of the tibia and changes in bone metabolism markers in ovariectomized rats. These results suggest caution in the use of NaF for the treatment of osteoporosis especially in postmenopausal woman(AU)