Maternal consumption of É·3 attenuates metabolic disruption elicited by saturated fatty acids-enriched diet in offspring rats.

BACKGROUND AND AIMS: High-fat diet (HFD) intake during gestation and lactation has been associated with an increased risk of developing cardiometabolic disorders in adult offspring. We investigated whether metabolic alterations resulting from the maternal consumption of HFD are prevented by the addition of omega-3 (É·3) in the diet. METHODS AND RESULTS: Wistar rat dams were fed a control (C: 19% of lipids and É·6:É·3 = 12), HF (HF: 33% lipids and É·6:É·3 = 21), or HF enriched with É·3 (HFω3: 33% lipids and É·6:É·3 = 9) diet during gestation and lactation, and their offspring food consumption, murinometric measurements, serum levels of metabolic markers, insulin and pyruvate sensitivity tests were evaluated. The maternal HFD increased body weight at birth, dyslipidemia, and elevated fasting glucose levels in the HF group. The enrichment of É·3 in the maternal HFD led to lower birth weight and improved lipid, glycemic, and transaminase biochemical profile of the HFω3 group until the beginning of adulthood. However, at later adulthood of the offspring, there was no improvement in these biochemical parameters. CONCLUSION: Our findings show the maternal consumption of high-fat É·3-rich diet is able to attenuate or prevent metabolic disruption elicited by HFD in offspring until 90 days old, but not in the long term, as observed at 300 days old of the offspring.

The probiotic Lactobacillus fermentum 296 attenuates cardiometabolic disorders in high fat diet-treated rats.

BACKGROUND AND AIM: High-fat (HF) diet consumption has been associated with gut dysbiosis and increased risk of dyslipidemia, type 2 diabetes mellitus and hypertension. Probiotic administration has been suggested as a safe therapeutic strategy for the treatment of cardiometabolic disorders. This study was designed to assess the effects of probiotic Lactobacillus (L.) fermentum 296, a fruit-derived bacteria strain, against cardiometabolic disorders induced by HF diet. METHODS AND RESULTS: Male Wistar rats were divided into control diet (CTL); HF diet; and HF diet treated with Lactobacillus fermentum 296 (HF + Lf 296). The L. fermentum 296 strain at 1 × 109 colony forming units (CFU)/ml were daily administered by oral gavage for 4 weeks. The results showed that rats fed with HF diet displayed insulin resistance, reduced Lactobacillus spp. counts in feces, serum lipids, and oxidative profile. Rats fed on HF diet also demonstrated augmented blood pressure associated with sympathetic hyperactivity and impaired baroreflex control. The administration of L. fermentum 296 for 4 weeks recovered fecal Lactobacillus sp. counts and alleviated hyperlipidemia, sympathetic hyperactivity, and reduced systolic blood pressure in HF rats without affecting baroreflex sensibility. CONCLUSION: Our results suggest the ability of L. fermentum 296 improve biochemical and cardiovascular parameters altered in cardiometabolic disorders.

Maternal protein restriction induced-hypertension is associated to oxidative disruption at transcriptional and functional levels in the medulla oblongata.

Maternal protein restriction during pregnancy and lactation predisposes the adult offspring to sympathetic overactivity and arterial hypertension. Although the underlying mechanisms are poorly understood, dysregulation of the oxidative balance has been proposed as a putative trigger of neural-induced hypertension. The aim of the study was to evaluate the association between the oxidative status at transcriptional and functional levels in the medulla oblongata and maternal protein restriction induced-hypertension. Wistar rat dams were fed a control (normal protein; 17% protein) or a low protein ((Lp); 8% protein) diet during pregnancy and lactation, and male offspring was studied at 90 days of age. Direct measurements of baseline arterial blood pressure (ABP) and heart rate (HR) were recorded in awakened offspring. In addition, quantitative RT-PCR was used to assess the mRNA expression of superoxide dismutase 1 (SOD1) and 2 (SOD2), catalase (CAT), glutathione peroxidase (GPx), Glutamatergic receptors (Grin1, Gria1 and Grm1) and GABA(A)-receptor-associated protein like 1 (Gabarapl1). Malondialdehyde (MDA) levels, CAT and SOD activities were examined in ventral and dorsal medulla. Lp rats exhibited higher ABP. The mRNA expression levels of SOD2, GPx and Gabarapl1 were down regulated in medullary tissue of Lp rats (P<.05, t test). In addition, we observed that higher MDA levels were associated to decreased SOD (approximately 45%) and CAT (approximately 50%) activities in ventral medulla. Taken together, our data suggest that maternal protein restriction induced-hypertension is associated with medullary oxidative dysfunction at transcriptional level and with impaired antioxidant capacity in the ventral medulla.

Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring.

BACKGROUND: Maternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms. OBJECTIVES: The aims of the study were to evaluate the effects of a low-protein (LP) diet during pregnancy and lactation on baseline sympathetic and respiratory activities and peripheral chemoreflex sensitivity in the rat offspring. METHODS: Wistar rat dams were fed a control [normal-protein (NP); 17% protein] or an LP (8% protein) diet during pregnancy and lactation, and their male offspring were studied at 30 d of age. Direct measurements of baseline arterial blood pressure (ABP), heart rate (HR), and respiratory frequency (Rf) as well as peripheral chemoreflex activation (potassium cyanide: 0.04%) were recorded in pups while they were awake. In addition, recordings of the phrenic nerve (PN) and thoracic sympathetic nerve (tSN) activities were obtained from the in situ preparations. Hypoxia-inducible factor 1α (HIF-1α) expression was also evaluated in carotid bifurcation through a Western blotting assay. RESULTS: At 30 d of age, unanesthetized LP rats exhibited enhanced resting Rf (P = 0.001) and similar ABP and HR compared with the NP rats. Despite their similar baseline ABP values, LP rats exhibited augmented low-frequency variability (∼91%; P = 0.01). In addition, the unanesthetized LP rats showed enhanced pressor (P = 0.01) and tachypnoeic (P = 0.03) responses to peripheral chemoreflex activation. The LP rats displayed elevated baseline tSN activity (∼86%; P = 0.02) and PN burst frequency (45%; P = 0.01) and amplitude (53%; P = 0.001) as well as augmented sympathetic (P = 0.01) and phrenic (P = 0.04) excitatory responses to peripheral chemoreflex activation compared with the NP group. Furthermore, LP rats showed an increase of ∼100% in HIF-1α protein density in carotid bifurcation compared with NP rats. CONCLUSION: Sympathetic-respiratory overactivity and amplified peripheral chemoreceptor responses, potentially through HIF-1α-dependent mechanisms, precede the onset of hypertension in juvenile rats exposed to protein undernutrition during gestation and lactation.

On the Aging Kinetics of a Flame-Resistant AZ91D-1.5%Ca Magnesium Alloy Processed with Ultrasonic Vibration.

The Mg-Al-Zn-Ca system has demonstrated excellent flame resistance and mechanical properties in the as-cast condition. However, the potential of these alloys to be heat-treated, e.g., by aging, as well as the influence of the initial microstructure on the precipitation kinetics, is yet to be comprehensively explored. Ultrasound treatment was applied during the solidification of an AZ91D-1.5%Ca alloy to promote microstructure refinement. Samples from treated and non-treated ingots were subjected to solution treatment at 415 °C for 480 min, followed by aging at 175 °C for up to 4920 min. The results showed that the ultrasound-treated material could reach the peak-age condition in a shorter period than the non-treated one, suggesting accelerated precipitation kinetics and, thus, enhanced aging response. However, the tensile properties showed a decrease in the peak age compared to the as-cast condition, probably due to the formation of precipitates at the grain boundaries that promote the formation of microcracks and intergranular early fracture. This research shows that tailoring the material's as-cast microstructure may positively affect its aging response, shortening the heat treatment duration, thereby making the process less expensive and more sustainable.

Analysis of ESAFORM 2021 cup drawing benchmark of an Al alloy, critical factors for accuracy and efficiency of FE simulations.

This article details the ESAFORM Benchmark 2021. The deep drawing cup of a 1 mm thick, AA 6016-T4 sheet with a strong cube texture was simulated by 11 teams relying on phenomenological or crystal plasticity approaches, using commercial or self-developed Finite Element (FE) codes, with solid, continuum or classical shell elements and different contact models. The material characterization (tensile tests, biaxial tensile tests, monotonic and reverse shear tests, EBSD measurements) and the cup forming steps were performed with care (redundancy of measurements). The Benchmark organizers identified some constitutive laws but each team could perform its own identification. The methodology to reach material data is systematically described as well as the final data set. The ability of the constitutive law and of the FE model to predict Lankford and yield stress in different directions is verified. Then, the simulation results such as the earing (number and average height and amplitude), the punch force evolution and thickness in the cup wall are evaluated and analysed. The CPU time, the manpower for each step as well as the required tests versus the final prediction accuracy of more than 20 FE simulations are commented. The article aims to guide students and engineers in their choice of a constitutive law (yield locus, hardening law or plasticity approach) and data set used in the identification, without neglecting the other FE features, such as software, explicit or implicit strategy, element type and contact model.

Inhaled iloprost as third add-on therapy in idiopathic pulmonary arterial hypertension.

Triple combination therapy is suggested in current pulmonary arterial hypertension guidelines in case of unsatisfactory treatment with oral double combination therapy. However, there is a lack of evidence concerning some of the drug combinations currently employed. We demonstrate the clinical and hemodynamical benefits of inhaled iloprost as third add-on therapy in idiopathic pulmonary arterial hypertension.

Central Inhibition of Tumor Necrosis Factor Alpha Reduces Hypertension by Attenuating Oxidative Stress in the Rostral Ventrolateral Medulla in Renovascular Hypertensive Rats.

Inflammation in the central nervous system is being considered a key player linked to neurogenic hypertension. Using combined in vivo and in vitro approaches, we investigated the effects of central inhibition of TNF-α on blood pressure, sympathetic tone, baroreflex sensitivity, and oxidative stress in the rostral ventrolateral medulla (RVLM) of rats with 2-kidney-1-clip (2K1C) renovascular hypertension. Continuous infusion of pentoxifylline, a TNF-α inhibitor, into the lateral ventricle of the brain for 14 consecutive days reduced blood pressure and improved baroreflex sensitivity in renovascular hypertensive rats. Furthermore, central TNF-α inhibition reduced sympathetic modulation and blunted the increased superoxide accumulation in the RVLM of 2K1C rats. Our findings suggest that TNF-α play an important role in the maintenance of sympathetic vasomotor tone and increased oxidative stress in the RVLM during renovascular hypertension.

Cancer-associated thrombosis: the when, how and why.

Cancer-associated thrombosis (CAT) is a condition in which relevance has been increasingly recognised both for physicians that deal with venous thromboembolism (VTE) and for oncologists. It is currently estimated that the annual incidence of VTE in patients with cancer is 0.5% compared to 0.1% in the general population. Active cancer accounts for 20% of the overall incidence of VTE. Of note, VTE is the second most prevalent cause of death in cancer, second only to the progression of the disease, and cancer is the most prevalent cause of deaths in VTE patients. Nevertheless, CAT presents several peculiarities that distinguish it from other VTE, both in pathophysiology mechanisms, risk factors and especially in treatment, which need to be considered. CAT data will be reviewed in this review.

A Newly Isolated Carboxymethyl-Glucan (CM-G) Restores Depressed Baroreflex Sensitivity in Renovascular Hypertensive Rats.

This study was designed to investigate the effects of a newly synthesized carboxymethyl-glucan (CM-G) on blood pressure (BP), baroreflex sensitivity (BRS) and sympathetic vascular modulation in renovascular hypertensive rats. Male Wistar rats were divided into four groups: Sham (n = 10); 2K1C (subjected to renal artery clipping to induce renovascular hypertension, n = 10); Sham + CM-G (treated with CM-G, n = 7) and 2K1C + CM-G (treated with CM-G, n = 7). The daily treatment with CM-G (40 mg/kg) was performed for 2 weeks. Blood pressure, heart rate (HR), systolic BP variability, baroreflex sensitivity (BRS) and sympathetic vascular tone were evaluated. After six weeks of renal artery clipping, 2K1C rats exhibited arterial hypertension (171 ± 11 vs. 118 ± 4 mmHg, p < 0.05), impaired BRS (-1.30 ± 0.10 vs. -2.59 ± 0.17 bpm.mmHg-1, p < 0.05) and enhanced sympathetic activity as shown by the hexamethonium test (-60 ± 5 vs. -33 ± 2 ΔmmHg, p < 0.05) when compared to sham rats. Oral administration of CM-G in renovascular hypertensive rats reduced hypertension (126 ± 4 vs. 171 ± 11 mmHg, p < 0.05) and improved the BRS (-2.03 ± 0.16 vs. -1.30 ± 0.10 bpm.mmHg-1, p < 0.05) in 2K1C rats when compared to placebo. Those effects seem to be caused by a reduction in sympathetic activity. The present study revealed for the first time that CM-G treatment reduces arterial hypertension and restores arterial baroreflex sensitivity via a reduction in the sympathetic tone in conscious renovascular hypertensive rats.

Glial Cells Are Involved in ANG-II-Induced Vasopressin Release and Sodium Intake in Awake Rats.

It is known that circulating angiotensin II (ANG-II) acts on the circumventricular organs (CVOs), which partially lack a normal blood-brain barrier, to stimulate pressor responses, vasopressin (AVP), and oxytocin (OT) secretion, as well as sodium and water intake. Although ANG-II type 1 receptors (AT1R) are expressed in neurons and astrocytes, the involvement of CVOs glial cells in the neuroendocrine, cardiovascular and behavioral responses induced by central ANG II remains to be further elucidated. To address this question, we performed a set of experiments combining in vitro studies in primary hypothalamic astrocyte cells (HACc) and in vivo intracerebroventricular (icv) microinjections into the lateral ventricle of awake rats. Our results showed that ANG-II decreased glutamate uptake in HACc. In addition, in vivo studies showed that fluorocitrate (FCt), a reversible glial inhibitor, increased OT secretion and mean arterial pressure (MAP) and decreased breathing at rest. Furthermore, previous FCt decreased AVP secretion and sodium intake induced by central ANG-II. Together, our findings support that CVOs glial cells are important in mediating neuroendocrine and cardiorespiratory functions, as well as central ANG-II-induced AVP release and salt-intake behavior in awake rats. In the light of our in vitro studies, we propose that these mechanisms are, at least in part, by ANG-II-induced astrocyte mediate reduction in glutamate extracellular clearance.

Structural monitoring and modeling of the mechanical deformation of three-dimensional printed poly(ε-caprolactone) scaffolds.

Three-dimensional (3D) printed poly(ε-caprolactone) (PCL) based scaffolds have being proposed for different tissue engineering applications. This study addresses the design and fabrication of 3D PCL constructs with different struts alignments at 90°, 45° and 90° with offset. The morphology and the mechanical behavior under uniaxial compressive load were assessed at different strain percentages. The combination of a new compressionCT device and micro computed tomography (micro-CT) allowed understanding the influence of pore geometry under controlled compressive strain in the mechanical and structural behavior of PCL constructs. Finite element analysis (FEA) was applied using the micro-CT data to modulate the mechanical response and compare with the conventional uniaxial compression tests. Scanning electron microscopic analysis showed a very high level of reproducibility and a low error comparing with the theoretical values, confirming that the alignment and the dimensional features of the printed struts are reliable. The mechanical tests showed that the 90° architecture presented the highest stiffness. With the compressionCT device was observed that the 90° and 90° with offset architectures presented similar values of porosity at same strain and similar pore size, contrary to the 45° architecture. Thus, pore geometric configurations affected significantly the deformability of the all PCL scaffolds under compression. The prediction of the FEA showed a good agreement to the conventional mechanical tests revealing the areas more affected under compression load. The methodology proposed in this study using 3D printed scaffolds with compressionCT device and FEA is a framework that offers great potential in understanding the mechanical and structural behavior of soft systems for different applications, including for the biomedical engineering field.

New Insights on the Use of Dietary Polyphenols or Probiotics for the Management of Arterial Hypertension.

Arterial hypertension (AH) is one of the most prevalent risk factors for cardiovascular diseases (CD) and is the main cause of deaths worldwide. Current research establish that dietary polyphenols may help to lower blood pressure (BP), thus contributing to the reduction of cardiovascular complications. In addition, the health benefits of probiotics on BP have also attracted increased attention, as probiotics administration modulates the microbiota, which, by interacting with ingested polyphenols, controls their bioavalability. The aim of the present mini-review is to summarize and clarify the effects of dietary polyphenols and probiotics administration on BP using combined evidence from clinical and experimental studies, as well as to discuss the current debate in the literature about the usefulness of this nutritional approach to manage BP. Clinical trials and experimental studies have demonstrated that consuming dietary polyphenols or probiotics in adequate amounts may improve BP, ranging from modest to greater effects. However, the mechanisms linking probiotic intake and reduced BP levels need to be further elucidated as a definitive consensus on the link between intake of polyphenols or probiotics and improvement of AH has not been reached yet.

New Insights on the Maternal Diet Induced-Hypertension: Potential Role of the Phenotypic Plasticity and Sympathetic-Respiratory Overactivity.

Systemic arterial hypertension (SAH) is an important risk factor for cardiovascular disease and affects worldwide population. Current environment including life style coupled with genetic programming have been attributed to the rising incidence of hypertension. Besides, environmental conditions during perinatal development such as maternal malnutrition can program changes in the integration among renal, neural, and endocrine system leading to hypertension. This phenomenon is termed phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental stimuli without genetic change, following a novel or unusual input during development. Human and animal studies indicate that fetal exposure to an adverse maternal environment may alter the renal morphology and physiology that contribute to the development of hypertension. Recently, it has been shown that the maternal protein restriction alter the central control of SAH by a mechanism that include respiratory dysfunction and enhanced sympathetic-respiratory coupling at early life, which may contribute to adult hypertension. This review will address the new insights on the maternal diet induced-hypertension that include the potential role of the phenotypic plasticity, specifically the perinatal protein malnutrition, and sympathetic-respiratory overactivity.