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Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO 2 , 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

(1) Background: The role of the nurse case manager is unknown to the population. The main objective is to analyze the existing differences within the national territory in order to make known the situation in Spain with a view to the recognition of its functions and the creation of the professional profile in an equal manner. (2) Methods: A scoping review was conducted in order to achieve the main aim. Selected articles were subjected to a critical reading, and the levels of evidence and grades of recommendation of the Joanna Briggs Institute were verified. The search field was limited to the last ten years. (3) Results: Case management models are heterogeneous in different autonomous communities in Spain. Case nurse management is qualified for high-complexity patients, follow up on chronic patients, and coordinate health assistance. (4) Conclusions: It concludes that nursing's role is crucial in the field of case management, being required in the follow-up of chronic patients of high complexity. Despite the proven health benefits, efficacy, and efficiency of case management, there are many heterogeneous models that coexist in Spain. This involves a restriction in the development of a nursing career because of the lack of a definition of its functions and competences.

Background/aim: Resistant triple-negative breast cancer (TNBC) is a subtype of this disease that is resistant to conventional chemotherapy agents. IFN-τ is a cytokine that has recently been shown to have immunoregulatory and antitumor effects. The present study aimed to examine the antiproliferative and apoptosis effects of IFN-τ in breast cancer cells and the antitumor effect in a murine tumor model of TNBC., Materials and Methods: Murine breast cancer 4T1 cells were cultured and treated with ovine IFN-τ and through MTT and Caspase-Glo 3/7 assays, viability and cell death were determined. In addition, the antitumor effect of IFN-τ was determined in a murine tumor model of TNBC., Results: Ovine IFN-τ showed a concentration-dependent antiproliferative effect on 4T1 murine breast cancer cells. Also, treatment of 4T1 cells with IFN-τ induced the activation of caspase 3 and 7, which is indicative of apoptotic cell death. Moreover, we detected an increase in the expression of type I interferon receptor (IFNAR1/2) in cells treated with IFN-. The intratumoral application of IFN-τ in mice inhibited tumor growth compared to the control non-treated group, and the effect was associated with the increased expression of GM-CSF., Conclusion: Ovine IFN-τ may be an effective immunotherapeutic cytokine for the treatment of TNBC., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The association between obstructive sleep apnea (OSA) and metabolic disorders is well-established; however, the underlying mechanisms that elucidate this relationship remain incompletely understood. Since the liver is a major organ in the maintenance of metabolic homeostasis, we hypothesize that liver dysfunction plays a crucial role in the pathogenesis of metabolic dysfunction associated with obstructive sleep apnea (OSA). Herein, we explored the underlying mechanisms of this association within the liver. Experiments were performed in male Wistar rats fed with a control or high fat (HF) diet (60% lipid-rich) for 12 weeks. Half of the groups were exposed to chronic intermittent hypoxia (CIH) (30 hypoxic (5% O 2 ) cycles, 8 h/day) that mimics OSA, in the last 15 days. Insulin sensitivity and glucose tolerance were assessed. Liver samples were collected for evaluation of lipid deposition, insulin signaling, glucose homeostasis, hypoxia, oxidative stress, antioxidant defenses, mitochondrial biogenesis and inflammation. Both the CIH and HF diet induced dysmetabolism, a state not aggravated in animals submitted to HF plus CIH. CIH aggravates hepatic lipid deposition in obese animals. Hypoxia-inducible factors levels were altered by these stimuli. CIH decreased the levels of oxidative phosphorylation complexes in both groups and the levels of SOD-1. The HF diet reduced mitochondrial density and hepatic antioxidant capacity. The CIH and HF diet produced alterations in cysteine-related thiols and pro-inflammatory markers. The results obtained suggest that hepatic mitochondrial dysfunction and oxidative stress, leading to inflammation, may be significant factors contributing to the development of dysmetabolism associated with OSA.

This research aimed to characterize the physicochemical, in vitro digestion, and structural features of digestion residues of maize and sorghum starches subjected to thermoplastic extrusion, along with the influence of Sodium Stearoyl Lactylate (SSL), to obtain improved starches for food applications and to understand their behavior when consumed as a food ingredient. The morphology of the extruded materials showed remanent starch granules when SSL was used. A higher amount of medium and large linear glucan chains were found in these particles, influencing higher thermal stability (ΔH ≈ 4 J/g) and a residual crystallinity arrangement varying from 7 to 17% in the extrudates. Such structural features were correlated with their digestibility, where slowly digestible starch (SDS) and resistant starch (RS) fractions ranged widely (from 18.28 to 27.88% and from 0.13 to 21.41%, respectively). By analyzing the data with a Principal component analysis (PCA), we found strong influences of B2 and B3 type chains on the thermal stability of the extrudates. The amylose and smaller glucan chains (A and B1) also significantly affected the emulsifying and foam stability properties. This research contributes to the molecular knowledge of starch in extruded products with broad food applications.

Hypoxia may be associated with alterations in bone remodeling, but the published results are contradictory. The aim of this study was to characterize the bone morphometry changes subject to hypoxia for a better understanding of the bone response to hypoxia and its possible clinical consequences on the bone metabolism. This study analyzed the bone morphometry parameters by micro-computed tomography (μCT) in rat and guinea pig normobaric hypoxia models. Adult male and female Wistar rats were exposed to chronic hypoxia for 7 and 15 days. Additionally, adult male guinea pigs were exposed to chronic hypoxia for 15 days. The results showed that rats exposed to chronic constant and intermittent hypoxic conditions had a worse trabecular and cortical bone health than control rats (under a normoxic condition). Rats under chronic constant hypoxia were associated with a more deteriorated cortical tibia thickness, trabecular femur and tibia bone volume over the total volume (BV/TV), tibia trabecular number (Tb.N), and trabecular femur and tibia bone mineral density (BMD). In the case of chronic intermittent hypoxia, rats subjected to intermittent hypoxia had a lower cortical femur tissue mineral density (TMD), lower trabecular tibia BV/TV, and lower trabecular thickness (Tb.Th) of the tibia and lower tibia Tb.N. The results also showed that obese rats under a hypoxic condition had worse values for the femur and tibia BV/TV, tibia trabecular separation (Tb.Sp), femur and tibia Tb.N, and BMD for the femur and tibia than normoweight rats under a hypoxic condition. In conclusion, hypoxia and obesity may modify bone remodeling, and thus bone microarchitecture, and they might lead to reductions in the bone strength and therefore increase the risk of fragility fracture.

(1) Background: The aim of this study was to explore the role of perceived stress and the health locus of control in Crohn's disease and their influence upon the development of flare-ups of this disease. (2) Methods: Stress and the external locus of control were evaluated in a sample of 64 Crohn's patients (flare-up phase versus latency phase). The perceived stress scale (PSS-14) and the multidimensional health locus of control scale were the measurement instruments used. (3) Results: The results indicate that the patients have high stress levels during a flare-up (26.13; 27.44; 28.79; 29.67); high stress levels (28.07; 29.67; 27.44; 28.07) if they have a high external locus of control; and that the external locus of control and stress levels have a significant influence upon the existence of flare-ups in those patients with low external locus of control levels (χ2 = 11.127; df = 1: p < 0.001). (4) Conclusions: Actions aimed at reducing stress and external locus of control levels are necessary in Crohn's disease.

Brewers' spent grain (BSG) is the most abundant byproduct generated from the beer-brewing process. BSG is a material rich in hemicellulose, composed of arabinoxylans (AX). However, the high crosslinking of this material causes low availability of AX, for which it is necessary to apply different treatments. The objective of this research is to increase the release of arabinoxylans through solid-state fermentation with Fusarium oxysporum f. sp. lycopersici using extruded brewery spent grain. First, the BSG is subjected to two types of physical treatments: extrusion at 20% moisture, 200 rpm and 50 °C (BSGe), and blade milling (BSGm). The chemical composition is determined for each sample (BSG, BSGe and BSGm). Subsequently, the solid-state fermentation process (SSF) is carried out on each sample. The fermentation kinetics at 30 °C are monitored for 7 days. Once the SSF concludes, AX are extracted, and the purity of AX is determined by the phloroglucinol colorimetric assay. Finally, the total phenolic compounds, phenolic acids and antioxidant capacity by DPPH are quantified. No significant differences ( p ≥ 0.05) in the protein, lipid, ash or total dietary fiber contents are found among the samples. No significant difference ( p ≥ 0.05) in the content of soluble fiber is found, although BSGe and BSGm have higher values than BSG. On the other hand, the yields of soluble AX exhibit significant differences ( p ≤ 0.05) among nonfermented samples (BSG, 0.03%; BSGm, 0.53%; BSGe, 0.70%) and with SSF (BSG, 2.95%; BSGm, 6.24%; and BSGe, 9.58%). In addition, the contents of free phenolic compounds and free phenolic acids and the percent inhibition of free extracts by 2,2-diphenyl-1-picrylhydrazyl (DPPH) differ significantly ( p ≤ 0.05) between samples subjected to SSF and nonfermented samples. Therefore, extrusion and SSF treatment increase AX release from BSG as well as the antioxidant capacity of the extracts.

Chronic sustained hypoxia (CSH), as found in individuals living at a high altitude or in patients suffering respiratory disorders, initiates physiological adaptations such as carotid body stimulation to maintain oxygen levels, but has deleterious effects such as pulmonary hypertension (PH). Obstructive sleep apnea (OSA), a respiratory disorder of increasing prevalence, is characterized by a situation of chronic intermittent hypoxia (CIH). OSA is associated with the development of systemic hypertension and cardiovascular pathologies, due to carotid body and sympathetic overactivation. There is growing evidence that CIH can also compromise the pulmonary circulation, causing pulmonary hypertension in OSA patients and animal models. The aim of this work was to compare hemodynamics, vascular contractility, and L-arginine-NO metabolism in two models of PH in rats, associated with CSH and CIH exposure. We demonstrate that whereas CSH and CIH cause several common effects such as an increased hematocrit, weight loss, and an increase in pulmonary artery pressure (PAP), compared to CIH, CSH seems to have more of an effect on the pulmonary circulation, whereas the effects of CIH are apparently more targeted on the systemic circulation. The results suggest that the endothelial dysfunction evident in pulmonary arteries with both hypoxia protocols are not due to an increase in methylated arginines in these arteries, although an increase in plasma SDMA could contribute to the apparent loss of basal NO-dependent vasodilation and, therefore, the increase in PAP that results from CIH.

The early stages of the COVID-19 pandemic presented the characteristics of a traumatic event that could trigger post-traumatic stress disorder. Emergency Medical Services workers are already a high-risk group due to their professional development. The research project aimed to analyse the impact of the COVID-19 pandemic on EMS professionals in terms of their mental health. For this purpose, we present a descriptive crosssectional study with survey methodology. A total of 317 EMS workers (doctors, nurses, and emergency medical technicians) were recruited voluntarily. Psychological distress, post-traumatic stress disorder, and insomnia were assessed. The instruments were the General Health Questionnaire-12 (GHQ-12), the Davidson Trauma Scale (DTS-8), and the Athens Insomnia Scale (AIS-8). We found that 36% of respondents had psychological distress, 30.9% potentially had PTSD, and 60.9% experienced insomnia. Years of work experience were found to be positively correlated, albeit with low effect, with the PTSD score ( r = 0.133). Finally, it can be stated that the COVID-19 pandemic has been a traumatic event for EMS workers. The number of professionals presenting psychological distress, possible PTSD, or insomnia increased dramatically during the early phases of the pandemic. This study highlights the need for mental health disorder prevention programmes for EMS workers in the face of a pandemic.

Several studies demonstrated a link between obstructive sleep apnea (OSA) and the development of insulin resistance. However, the main event triggering insulin resistance in OSA remains to be clarified. Herein, we investigated the effect of mild and severe chronic intermittent hypoxia (CIH) on whole-body metabolic deregulation and visceral adipose tissue dysfunction. Moreover, we studied the contribution of obesity to CIH-induced dysmetabolic states. Experiments were performed in male Wistar rats submitted to a control and high-fat (HF) diet. Two CIH protocols were tested: A mild CIH paradigm (5/6 hypoxic (5% O 2 ) cycles/h, 10.5 h/day) during 35 days and a severe CIH paradigm (30 hypoxic (5% O 2 ) cycles, 8 h/day) during 15 days. Fasting glycemia, insulinemia, insulin sensitivity, weight, and fat mass were assessed. Adipose tissue hypoxia, inflammation, angiogenesis, oxidative stress, and metabolism were investigated. Mild and severe CIH increased insulin levels and induced whole-body insulin resistance in control animals, effects not associated with weight gain. In control animals, CIH did not modify adipocytes perimeter as well as adipose tissue hypoxia, angiogenesis, inflammation or oxidative stress. In HF animals, severe CIH attenuated the increase in adipocytes perimeter, adipose tissue hypoxia, angiogenesis, and dysmetabolism. In conclusion, adipose tissue dysfunction is not the main trigger for initial dysmetabolism in CIH. CIH in an early stage might have a protective role against the deleterious effects of HF diet on adipose tissue metabolism.

(1) Background: The confinement of the population in response to the COVID-19 pandemic was related to an increased risk of suffering from anxiety and/or depression in previous studies with other populations. (2) Methods: descriptive study using surveys (Goldberg Anxiety and Depression Scale) with 808 participants over 18 years of age between 14 and 20 of May 2020 during the confinement due to the SARS-CoV-2 virus in Spain. (3) Results: 63% of the participants were at risk of suffering from anxiety and 64.9% were at risk of depression. Variables reaching statistical significance were: age (t anxiety = -0.139 and t depression = -0.153), gender (t anxiety = -4.152 and t depression = -4.178), marital status (anxiety F = 2.893 and depression F = 3.011), symptoms compatible with COVID-19 (t anxiety = -4.177 and t depression = -3.791), previous need for psychological help (t anxiety = -5.385 and t depression = -7.136) and need for such help at the time of the study (t anxiety = -9.144 and depression = -10.995). In addition, we generated two regression models that estimate the risk of anxiety and depression. (4) Conclusions: more than half of the participants were at risk of suffering from anxiety and/or depression, confirming the negative effect of confinement on the population.

Physicochemical and microbiological properties of pork chops sprayed with Neutral Electrolyzed Water (NEW) were evaluated during storage at refrigeration temperature. Pork chops were randomly allocated into three groups and were artificially contaminated with an inoculum of 10 6  CFU/mL of Listeria monocytogenes. Each group was treated with either NEW (58 ppm), NaClO (35 ppm), or saline solution (SS). Subsequently, recovered bacteria were plated on TSA petri dishes and the reduction percentage of Listeria monocytogenes was calculated 24 h and 8 days after treatment. Physicochemical analysis [pH, content of lactic acid, thiobarbituric acid reactive substances (TBARS) and total volatile base nitrogen (TVBN)] were performed to evaluate the effect of all solutions used on pork meat kept at 4 °C for 19 days. In vitro NEW reduced L. monocytogenes titers by > 99.98% and 80.19% and 90.35% in artificially contaminated pork 24 h and 8 days after NEW treatment, respectively. Compared to the SS treatment, NEW and NaClO solutions caused a 0.67 Log UFC/g and 0.65 Log UFC/g reduction respectively. After eight days post-treatment, NEW and NaClO bacterial titers were below the SS treatment. NEW caused little color change in treated meat. It helped to reduce the formation of lactic acid and TVB-N when pork chops are kept at 4 °C for 19 days. Therefore, NEW could be considered as a new alternative to sanitize and preserve pork meat.

The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO 2 patterns. In both situations, chronic intermittent hypoxia (CIH) exposure produces carotid body (CB) hyperactivation generating an increased input to the brainstem which originates sympathetic hyperactivity, followed by hypertension that is abolished by CB denervation. CB has dopamine (DA) receptors in chemoreceptor cells acting as DA-2 autoreceptors. The aim was to check if blocking DA-2 receptors could decrease the CB hypersensitivity produced by CIH, minimizing CIH-related effects. Domperidone (DOM), a selective peripheral DA-2 receptor antagonist that does not cross the blood-brain barrier, was used to examine its effect on CIH (30 days) exposed rats. Arterial pressure, CB secretory activity and whole-body plethysmography were measured. DOM, acute or chronically administered during the last 15 days of CIH, reversed the hypertension produced by CIH, an analogous effect to that obtained with CB denervation. DOM marginally decreased blood pressure in control animals and did not affect hypoxic ventilatory response in control or CIH animals. No adverse effects were observed. DOM, used as gastrokinetic and antiemetic drug, could be a therapeutic opportunity for hypertension in SAHS patients' resistant to standard treatments.

The mechanisms of signal transduction by interferon-tau (IFN-τ) are widely known during the gestation of ruminants. In trophoblast cells, IFN-τ involves the activation of the JAK-STAT pathway, and it can have effects on other cell types, such as tumor cells. Here we report that the HPV16-positive BMK-16/myc cell treated with ovine IFN-τ, results in the activation of the canonical JAK-STAT and non-canonical JAK-STAT pathway. The MAPK signaling pathway was activated, we detected the proteins MEK1, MEK2, Raf1, STAT3, STA4, STAT5 and STAT6. Moreover, IFN-τ induced the expression of MHC Class I, MX and IP10 in the tumor cells and this response may be associated with the viral replication and with the anti-proliferative and the immunoregulatory effects of IFN-τ., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Epidemiological studies showed that chronic caffeine intake decreased the risk of type 2 diabetes. Previously, we described that chronic caffeine intake prevents and reverses insulin resistance induced by hypercaloric diets and aging, in rats. Caffeine has several cellular mechanisms of action, being the antagonism of adenosine receptors the only attained with human coffee consumption. Here, we investigated the subtypes of adenosine receptors involved on the effects of chronic caffeine intake on insulin sensitivity and the mechanisms and sex differences behind this effect. Experiments were performed in male and female Wistar rats fed either a chow or high-sucrose (HSu) diet (35% of sucrose in drinking water) during 28 days, to induce insulin resistance. In the last 15 days of diet the animals were submitted to DPCPX (A 1 antagonist, 0.4 mg/kg), SCH58261 (A 2A antagonist, 0.5 mg/kg), or MRS1754 (A 2B antagonist, 9.5 μg/kg) administration. Insulin sensitivity, fasting glycaemia, blood pressure, catecholamines, and fat depots were assessed. Expression of A 1 , A 2A , A 2B adenosine receptors and protein involved in insulin signaling pathways were evaluated in the liver, skeletal muscle, and visceral adipose tissue. UCP1 expression was measured in adipose tissue. Paradoxically, SCH58261 and MRS1754 decreased insulin sensitivity in control animals, whereas they both improved insulin response in HSu diet animals. DPCPX did not alter significantly insulin sensitivity in control or HSu animals, but reversed the increase in total and visceral fat induced by the HSu diet. In skeletal muscle, A 1 , A 2A , and A 2B adenosine receptor expression were increased in HSu group, an effect that was restored by SCH58261 and MRS1754. In the liver, A 1 , A 2A expression was increased in HSu group, while A 2B expression was decreased, being this last effect reversed by administration of MRS1754. In adipose tissue, A 1 and A 2A block upregulated the expression of these receptors. A 2 adenosine antagonists restored impaired insulin signaling in the skeletal muscle of HSu rats, but did not affect liver or adipose insulin signaling. Our results show that adenosine receptors exert opposite effects on insulin sensitivity, in control and insulin resistant states and strongly suggest that A 2 adenosine receptors in the skeletal muscle are the majors responsible for whole-body insulin sensitivity., (Copyright © 2020 Sacramento, Martins, Rodrigues, Matafome, Ribeiro, Olea and Conde.)

Introduction: Older adults constitute the most vulnerable population group to the COVID-19 pandemic. In Mexico, their biopsychosocial conditions might intensify their vulnerability., Method: Affiliation to health systems, health conditions and gerontological evaluation of 3,218 older adults were analyzed following the methodology of the PAHO-Mexico Health, Well-being and Aging Survey., Results: 88.6 % of older adults referred being affiliated to health systems; 30.2 %, 52.4 %, 10.3 %, 4.1 % and 5.6 % referred suffering from diabetes mellitus, high blood pressure, chronic obstructive pulmonary disease, heart disease and cerebrovascular disease, respectively; 15.6 % reported urinary incontinence, and 11.3%, fecal incontinence; 12.1 % of the women referred having suffered from breast cancer at some point, and 6.3 %, cervical cancer. The habit of smoking tobacco was observed in 11.1 %, risk of malnutrition in 32.8 %, established malnutrition in 4.1 %, functional dependence for basic and instrumental activities of daily life in 16.3 % and 17.6 %, respectively., Conclusion: Comprehensive gerontological evaluation is essential for efficient care of older adults who suffer from COVID-19, and for adequate care of the effects or health conditions at the conclusion of the confinement imposed by the pandemic., (Copyright: © 2019 Permanyer.)

The pecan ( Carya illinoinensis ) nut shell is an important byproduct of the food processing industry that has not been previously explored as an antioxidant compound. This work aims to study the effect of the extrusion temperature and screw speed on the moisture content, water and oil absorption index, water solubility index, color, phenolic compounds, condensed tannin compounds, and antioxidant activity of pecan nut shell extrudates. Extrusion variables were adjusted using a response surface methodology. Extrusion, performed at 70 °C and 150 rpm, almost doubled the concentration of polyphenols in the non-extruded shell and significantly increased radical scavenging activity. Compounds in extrudates, performed at 70 °C and 150 rpm, were quantified by high-performance liquid chromatography (HPLC) with a diode-array detector (DAD) and identified by liquid chromatography coupled with time-of-flight mass spectrometry (LC-MSD-TOF). Extrusion significantly increased most phenolic acid compounds, including gallic acid, ellagic acid pentose, ellagic acid, dimethyl ellagic acid rhamnoside, and dimethyl ellagic acid. The soluble fiber in extrudates was more than three-fold higher than in the control. Therefore, extrusion at 70 °C and 150 rpm increased the concentration of phenolic compounds, antioxidant activity, and total dietary and soluble fiber. Our findings support the notion that extruded pecan nut shell can be used in clean-label products and improve their nutraceutical value.

Key Points: Adenosine and ATP are excitatory neurotransmitters involved in the carotid body (CB) response to hypoxia. During ageing the CB exhibits a decline in its functionality, demonstrated by decreased hypoxic responses. In aged rats (20-24 months old) there is a decrease in: basal and hypoxic release of adenosine and ATP from the CB; expression of adenosine and ATP receptors in the petrosal ganglion; carotid sinus nerve (CSN) activity in response to hypoxia; and ventilatory responses to ischaemic hypoxia. There is also an increase in SNAP25, ENT1 and CD73 expression. It is concluded that, although CSN activity and ventilatory responses to hypoxia decrease with age, adjustments in purinergic metabolism in the CB in aged animals are present aiming to maintain the contribution of adenosine and ATP. The possible significance of the findings in the context of ageing and in CB-associated pathologies is considered., Abstract: During ageing the carotid body (CB) exhibits a decline in its functionality. Here we investigated the effect of ageing on functional CB characteristics as well as the contribution of adenosine and ATP to CB chemosensory activity. Experiments were performed in 3-month-old and 20- to 24-month-old male Wistar rats. Ageing decreased: the number of tyrosine hydroxylase immune-positive cells, but not type II cells or nestin-positive cells in the CB; the expression of P2X 2 and A 2A receptors in the petrosal ganglion; and the basal and hypoxic release of adenosine and ATP from the CB. Ageing increased ecto-nucleotidase (CD73) immune-positive cells and the expression of synaptosome associated protein 25 (SNAP25) and equilibrative nucleoside transporter 1 (ENT1) in the CB. Additionally, ageing did not modify basal carotid sinus nerve (CSN) activity or the activity in response to hypercapnia, but decreased CSN activity in hypoxia. The contribution of adenosine and ATP to stimuli-evoked CSN chemosensory activity in aged animals followed the same pattern of 3-month-old animals. Bilateral common carotid occlusions during 5, 10 and 15 s increased ventilation proportionally to the duration of ischaemia, an effect decreased by ageing. ATP contributed around 50% to ischaemic-ventilatory responses in young and aged rats; the contribution of adenosine was dependent on the intensity of ischaemia, being maximal in ischaemias of 5 s (50%) and much smaller in 15 s ischaemias. Our results demonstrate that both ATP and adenosine contribute to CB chemosensory activity in ageing. Though CB responses to hypoxia, but not to hypercapnia, decrease with age, the relative contribution of both ATP and adenosine for CB activity is maintained., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Dry soybean ( Glycine max ) residue (SBR) is a byproduct rich in dietary fibre and protein with high levels of essential amino acids. The effects due to the substitution of refined wheat flour with 5% or 10% SBR in dough rheology and hot-press tortilla texture, dimensions, colour, protein and dietary fibre contents were studied. Substitution of 10% SBR improved flour in terms of gluten strength and sedimentation without significantly affecting dough hardness, cohesiveness, adhesiveness, and extensibility. The dimensions, colour and sensory acceptance of the supplemented tortillas were not affected by the addition of the SBR. The 10% SBR tortillas contained 1.77 times more insoluble dietary fibre, protein content of 9.3%, in vitro protein digestibility of 84% and protein digestibility corrected amino acid score (PDCAAS) of 52.63%. Results indicated that wheat flour tortillas with 10% SBR an excellent alternative to regular counterparts owing to their higher dietary fibre and protein quantity and quality., Competing Interests: Compliance with ethical standardsAll authors have not conflict of interest to declare.

Key Points: Leptin plays a role in the control of breathing, acting mainly on central nervous system; however, leptin receptors have been recently shown to be expressed in the carotid body (CB), and this finding suggests a physiological role for leptin in the regulation of CB function. Leptin increases minute ventilation in both basal and hypoxic conditions in rats. It increases the frequency of carotid sinus nerve discharge in basal conditions, as well as the release of adenosine from the CB. However, in a metabolic syndrome animal model, the effects of leptin in ventilatory control, carotid sinus nerve activity and adenosine release by the CB are blunted. Although leptin may be involved in triggering CB overactivation in initial stages of obesity and dysmetabolism, resistance to leptin signalling and blunting of responses develops in metabolic syndrome animal models., Abstract: Leptin plays a role in the control of breathing, acting mainly on central nervous system structures. Leptin receptors are expressed in the carotid body (CB) and this finding has been associated with a putative physiological role of leptin in the regulation of CB function. Since, the CBs are implicated in energy metabolism, here we tested the effects of different concentrations of leptin administration on ventilatory parameters and on carotid sinus nerve (CSN) activity in control and high-fat (HF) diet fed rats, in order to clarify the role of leptin in ventilation control in metabolic disease states. We also investigated the expression of leptin receptors and the neurotransmitters involved in leptin signalling in the CBs. We found that in non-disease conditions, leptin increases minute ventilation in both basal and hypoxic conditions. However, in the HF model, the effect of leptin in ventilatory control is blunted. We also observed that HF rats display an increased frequency of CSN discharge in basal conditions that is not altered by leptin, in contrast to what is observed in control animals. Leptin did not modify intracellular Ca 2+ in CB chemoreceptor cells, but it produced an increase in the release of adenosine from the whole CB. We conclude that CBs represent an important target for leptin signalling, not only to coordinate peripheral ventilatory chemoreflexive drive, but probably also to modulate metabolic variables. We also concluded that leptin signalling is mediated by adenosine release and that HF diets blunt leptin responses in the CB, compromising ventilatory adaptation., (© 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.)

Clinical and experimental evidence indicates a positive correlation between chronic intermittent hypoxia (CIH), increased carotid body (CB) chemosensitivity, enhanced sympatho-respiratory coupling and arterial hypertension and cardiovascular disease. Several groups have reported that both the afferent and efferent arms of the CB chemo-reflex are enhanced in CIH animal models through the oscillatory CB activation by recurrent hypoxia/reoxygenation episodes. Accordingly, CB ablation or denervation results in the reduction of these effects. To date, no studies have determined the effects of CIH treatment in chemo-reflex sensitization in guinea pig, a rodent with a hypofunctional CB and lacking ventilatory responses to hypoxia. We hypothesized that the lack of CB hypoxia response in guinea pig would suppress chemo-reflex sensitization and thereby would attenuate or eliminate respiratory, sympathetic and cardiovascular effects of CIH treatment. The main purpose of this study was to assess if guinea pig CB undergoes overactivation by CIH and to correlate CIH effects on CB chemoreceptors with cardiovascular and respiratory responses to hypoxia. We measured CB secretory activity, ventilatory parameters, systemic arterial pressure and sympathetic activity, basal and in response to acute hypoxia in two groups of animals: control and 30 days CIH exposed male guinea pigs. Our results indicated that CIH guinea pig CB lacks activity elicited by acute hypoxia measured as catecholamine (CA) secretory response or intracellular calcium transients. Plethysmography data showed that only severe hypoxia (7% O 2 ) and hypercapnia (5% CO 2 ) induced a significant increased ventilatory response in CIH animals, together with higher oxygen consumption. Therefore, CIH exposure blunted hyperventilation to hypoxia and hypercapnia normalized to oxygen consumption. Increase in plasma CA and superior cervical ganglion CA content was found, implying a CIH induced sympathetic hyperactivity. CIH promoted cardiovascular adjustments by increasing heart rate and mean arterial blood pressure without cardiac ventricle hypertrophy. In conclusion, CIH does not sensitize CB chemoreceptor response to hypoxia but promotes cardiovascular adjustments probably not mediated by the CB. Guinea pigs could represent an interesting model to elucidate the mechanisms that underlie the long-term effects of CIH exposure to provide evidence for the role of the CB mediating pathological effects in sleep apnea diseases.

Mammals have developed different mechanisms to maintain oxygen supply to cells in response to hypoxia. One of those mechanisms, the carotid body (CB) chemoreceptors, is able to detect physiological hypoxia and generate homeostatic reflex responses, mainly ventilatory and cardiovascular. It has been reported that guinea pigs, originally from the Andes, have a reduced ventilatory response to hypoxia compared to other mammals, implying that CB are not completely functional, which has been related to genetically/epigenetically determined poor hypoxia-driven CB reflex. This study was performed to check the guinea pig CB response to hypoxia compared to the well-known rat hypoxic response. These experiments have explored ventilatory parameters breathing different gases mixtures, cardiovascular responses to acute hypoxia, in vitro CB response to hypoxia and other stimuli and isolated guinea pig chemoreceptor cells properties. Our findings show that guinea pigs are hypotensive and have lower arterial pO 2 than rats, probably related to a low sympathetic tone and high hemoglobin affinity. Those characteristics could represent a higher tolerance to hypoxic environment than other rodents. We also find that although CB are hypo-functional not showing chronic hypoxia sensitization, a small percentage of isolated carotid body chemoreceptor cells contain tyrosine hydroxylase enzyme and voltage-dependent K + currents and therefore can be depolarized. However hypoxia does not modify intracellular Ca 2+ levels or catecholamine secretion. Guinea pigs are able to hyperventilate only in response to intense acute hypoxic stimulus, but hypercapnic response is similar to rats. Whether other brain areas are also activated by hypoxia in guinea pigs remains to be studied.

Aims/hypothesis: We recently described that carotid body (CB) over-activation is involved in the aetiology of insulin resistance and arterial hypertension in animal models of the metabolic syndrome. Additionally, we have demonstrated that CB activity is increased in animal models of insulin resistance, and that carotid sinus nerve (CSN) resection prevents the development of insulin resistance and arterial hypertension induced by high-energy diets. Here, we tested whether the functional abolition of CB by CSN transection would reverse pre-established insulin resistance, dyslipidaemia, obesity, autonomic dysfunction and hypertension in animal models of the metabolic syndrome. The effect of CSN resection on insulin signalling pathways and tissue-specific glucose uptake was evaluated in skeletal muscle, adipose tissue and liver., Methods: Experiments were performed in male Wistar rats submitted to two high-energy diets: a high-fat diet, representing a model of insulin resistance, hypertension and obesity, and a high-sucrose diet, representing a lean model of insulin resistance and hypertension. Half of each group was submitted to chronic bilateral resection of the CSN. Age-matched control rats were also used., Results: CSN resection normalised systemic sympathetic nervous system activity and reversed weight gain induced by high-energy diets. It also normalised plasma glucose and insulin levels, insulin sensitivity lipid profile, arterial pressure and endothelial function by improving glucose uptake by the liver and perienteric adipose tissue., Conclusions/interpretation: We concluded that functional abolition of CB activity restores insulin sensitivity and glucose homeostasis by positively affecting insulin signalling pathways in visceral adipose tissue and liver.

Objective and Methods: Diabetes mellitus (DM) is a global health problem, which significantly affects older adults. . The prevalence and biopsychosocial conditions of DM in older adults in the State of Hidalgo, Mexico, are analyzed using the Health and Aging Survey 2014 (SABE-Hidalgo, Mexico)., Results: DM in older adults presents a prevalence of 28.22% in the State, predominating in women and becoming more common with increasing age. The highest frequency occurs in residents of urban areas (57.2%), those with less schooling (79.6%), and those who live with relatives (77%). In addition, 54.7% of older adults with DM had cognitive impairment, 67.9% had arterial hypertension and 45.28% presented joint disease. 41.2% suffered falls, 68.52% visual problems and 87.3% tooth loss. Finally, 85.8% receive care but only 29.2% perceive improvement in their health., Conclusions: It is fundamental to develop integral programs and policies to care for older adults with DM., (Copyright: © 2017 SecretarÍa de Salud)

Key Points: Adult animals that have been perinatally exposed to oxygen-rich atmospheres (hyperoxia), recalling those used for oxygen therapy in infants, exhibit a loss of hypoxic pulmonary vasoconstriction, whereas vasoconstriction elicited by depolarizing agents is maintained. Loss of pulmonary hypoxic vasoconstriction is not linked to alterations in oxygen-sensitive K(+) currents in pulmonary artery smooth muscle cells. Loss of hypoxic vasoconstriction is associated with early postnatal oxidative damage and corrected by an antioxidant diet. Perinatal hyperoxia damages carotid body chemoreceptor cell function and the antioxidant diet does not reverse it. The hypoxia-elicited increase in erythropoietin plasma levels is not affected by perinatal hyperoxia. The potential clinical significance of the findings in clinical situations such as pneumonia, chronic obstructive pulmonary disease or general anaesthesia is considered., Abstract: Adult mammalians possess three cell systems that are activated by acute bodily hypoxia: pulmonary artery smooth muscle cells (PASMC), carotid body chemoreceptor cells (CBCC) and erythropoietin (EPO)-producing cells. In rats, chronic perinatal hyperoxia causes permanent carotid body (CB) atrophy and functional alterations of surviving CBCC. There are no studies on PASMC or EPO-producing cells. Our aim is to define possible long-lasting functional changes in PASMC or EPO-producing cells (measured as EPO plasma levels) and, further, to analyse CBCC functional alterations. We used 3- to 4-month-old rats born and reared in a normal atmosphere or exposed to perinatal hyperoxia (55-60% O2 for the last 5-6 days of pregnancy and 4 weeks after birth). Perinatal hyperoxia causes an almost complete loss of hypoxic pulmonary vasoconstriction (HPV), which was correlated with lung oxidative status in early postnatal life and prevented by antioxidant supplementation in the diet. O2 -sensitivity of K(+) currents in the PASMC of hyperoxic animals is normal, indicating that their inhibition is not sufficient to trigger HPV. Perinatal hyperoxia also abrogated responses elicited by hypoxia on catecholamine and cAMP metabolism in the CB. An increase in EPO plasma levels elicited by hypoxia was identical in hyperoxic and control animals, implying a normal functioning of EPO-producing cells. The loss of HPV observed in adult rats and caused by perinatal hyperoxia, comparable to oxygen therapy in premature infants, might represent a previously unrecognized complication of such a medical intervention capable of aggravating medical conditions such as regional pneumonias, atelectases or general anaesthesia in adult life., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Second-generation bioethanol production from sweet sorghum bagasse first extruded at different conditions and then treated with cell wall degrading enzymes and fermented with I. orientalis was determined. The twin extruder parameters tested were barrel temperature, screws speed, and feedstock moisture content using surface response methodology. The best extrusion conditions were 100°C, 200 rpm, and 30% conditioning moisture content. This nonchemical and continuous pretreatment did not generate inhibitory compounds. The extruded feedstocks were saccharified varying the biocatalysis time and solids loading. The best conditions were 20% solids loading and 72 h of enzymatic treatment. These particular conditions converted 70% of the total fibrous carbohydrates into total fermentable C5 and C6 sugars. The extruded enzymatically hydrolyzed sweet sorghum bagasse was fermented with the strain I. orientalis at 12% solids obtaining a yield of 198.1 mL of ethanol per kilogram of bagasse (dw).

Obstructive sleep apnea (OSA) consists of sleep-related repetitive obstructions of upper airways that generate episodes of recurrent or intermittent hypoxia (IH). OSA commonly generates cardiovascular and metabolic pathologies defining the obstructive sleep apnea syndrome (OSAS). Literature usually links OSA-associated pathologies to IH episodes that would cause an oxidative status and a carotid body-mediated sympathetic hyperactivity. Because cardiovascular and metabolic pathologies in obese patients and those with OSAS are analogous, we used models (24-wk-old Wistar rats) of IH (applied from weeks 22 to 24) and diet-induced obesity (O; animals fed a high-fat diet from weeks 12 to 24) to define the effect of each individual maneuver and their combination on the oxidative status and sympathetic tone of animals, and to quantify cardiovascular and metabolic parameters and their deviation from normality. We found that IH and O cause an oxidative status (increased lipid peroxides and diminished activities of superoxide dismutases), an inflammatory status (augmented C-reactive protein and nuclear factor kappa-B activation), and sympathetic hyperactivity (augmented plasma and renal artery catecholamine levels and synthesis rate); combined treatments worsened those alterations. IH and O augmented liver lipid content and plasma cholesterol, triglycerides, leptin, glycemia, insulin levels, and HOMA index, and caused hypertension; most of these parameters were aggravated when IH and O were combined. IH diminished ventilatory response to hypoxia, and hypercapnia and O created a restrictive ventilatory pattern; a combination of treatments led to restrictive hypoventilation. Data demonstrate that IH and O cause comparable metabolic and cardiovascular pathologies via misregulation of the redox status and sympathetic hyperactivity., (Copyright © 2014 the American Physiological Society.)

When de Castro entered the carotid body (CB) field, the organ was considered to be a small autonomic ganglion, a gland, a glomus or glomerulus, or a paraganglion. In his 1928 paper, de Castro concluded: "In sum, the Glomus caroticum is innervated by centripetal fibers, whose trophic centers are located in the sensory ganglia of the glossopharyngeal, and not by centrifugal [efferent] or secretomotor fibers as is the case for glands; these are precisely the facts which lead to suppose that the Glomus caroticum is a sensory organ." A few pages down, de Castro wrote: "The Glomus represents an organ with multiple receptors furnished with specialized receptor cells like those of other sensory organs [taste buds?]…As a plausible hypothesis we propose that the Glomus caroticum represents a sensory organ, at present the only one in its kind, dedicated to capture certain qualitative variations in the composition of blood, a function that, possibly by a reflex mechanism would have an effect on the functional activity of other organs… Therefore, the sensory fiber would not be directly stimulated by blood, but via the intermediation of the epithelial cells of the organ, which, as their structure suggests, possess a secretory function which would participate in the stimulation of the centripetal fibers." In our article we will recreate the experiments that allowed Fernando de Castro to reach this first conclusion. Also, we will scrutinize the natural endowments and the scientific knowledge that drove de Castro to make the triple hypotheses: the CB as chemoreceptor (variations in blood composition), as a secondary sensory receptor which functioning involves a chemical synapse, and as a center, origin of systemic reflexes. After a brief account of the systemic reflex effects resulting from the CB stimulation, we will complete our article with a general view of the cellular-molecular mechanisms currently thought to be involved in the functioning of this arterial chemoreceptor.

Objective: To determine the efficacy and tolerability of a long-acting dihydropyridine in the clinical settings of general practice., Material and Methods: 110 essential hypertensives were included (age 62.3 +/- 10.8 years, 51 men and 53 women, 38/ obese -IMC >30 kg/m2, ten diabetics). 104 patients ended the followup. Patients were treated with lercanidipine 10 mg once daily in the morning. Follow-up lasted 6 months. When blood pressure was not controlled (BP < 140/90 mmHg) in any visit, a second drug was added, excluding calcium channel blockers. Antiadrenergic drugs were recommended. If patients were not controlled ittwo consecutive visits they were excluded from follow-up., Results: Significant reductions in both systolic (baseline 157.4 +/- 11.7 vs 131.1 +/- 6.8 mmHg, p < 0,001) and diastolic BP (baseline 94.7 +/- 5.8 vs 80.0 +/- 5.5 mmHg, p < 0,001) were attained at six months. Mean SBP decrease was 26.7 mmHg and mean DBP reduction was 15.6 mmHg. At the study end, 84.3/ of the patients achieved a BP < 140/90 mmHg. Thirty patients needed a second drug to become controlled (26 at the study end). The overall incidence of adverse effects was 4,4/ (n=6) and just three patients withdrew the treatment due to untoward effects. Plasmatic cholesterol lowered from 225.3 +/- 41.0 to 216.7 +/- 25.3 mg/dl (p = 0,03) and urate decreased from 5.6 +/- 1.6 to 5.1 +/- 1.4 mgldl, p = 0,03)., Conclusions: Lercanidipine is a calcium channel blockers of high efficacy and low incidence of adverse effects in the clinical settings of general practice. It seems to have a positive metabolic effects on plasmatic levels of cholesterol and urate.