Impact of sound levels on physiological and consciousness state of cardiovascular patients

This research received specific grants from the Regional Ministry of Health and Families, Government of Andalusia. Reference: PIGE-0462-2019. Principal investigator: Morales-Cané I/Reference: PI-0360-2017. Principal investigator: López-Soto PJ.ETHICS STATEMENT The project was approved by the reference research ethics committee (Act no. 277, reference 3878) and carried out in accordance with the ethical principles established in the Declaration of Helsinki on Human Rights and Biomedicine, as well as the Spanish legislation on personal data protection.Background Patients treated in intensive care units (ICUs) experience life-threatening medical conditions but some external factors in ICUs do not help or even adversely affect and complicate their evolution. Among others, such factors include noise pollution due to alarms and medical clinical equipment, as well as the activities of the health care personnel themselves. Aim This study aimed to evaluate the influence of elevated sound levels on physiological variables and the consciousness state of patients treated in a cardiovascular area in an ICU. Design A longitudinal study with several observations was carried out during 1 month in the cardiovascular area of an ICU of a third-level hospital in southern Spain. Methods Sound levels were monitored in different work shifts and patients' physiological data and consciousness status were recorded. Generalized additive mixed models (GAMMs) were developed to detect the variability of the sound levels together with the vital parameters of the patients in the ICU. Results Thirty-eight patients were included. The mean sound level was 54.09 dBA. The GAMM sound levels analysis showed a significant increase in sound levels from 4:30 p.m. to 8:00 p.m. (1.83 dBA; P < .001) and 8:00 p.m. to 11:30 p.m. (3.06 dBA; P < .001). An increase in heart rate (3.66 bpm; P < .001), respiratory rate (2.62 rpm; P < .001) and the Glasgow Coma Scale (0.50 units; P = .002) was detected during the 4:30 p.m.–8:30 p.m. period. Conclusions Elevated sound levels in cardiovascular ICUs seem to influence positively the physiological and consciousness status of patients. Given the importance of the findings for patient safety, future intervention studies are recommended. Relevance to Clinical Practice The finding of this study could translate into structural changes in ICU facilities, as well as the development of clinical practice guidelines that influence the behaviour of health care professionals.Regional Ministry of Health and Families, Government of Andalusia. Reference: PIGE-0462-201

Changes in plasma susceptibility to lipid peroxidation and vitamin C in preterm and full-term neonates

Introduction: This study was designed to compare the plasma lipid peroxidation (LPO) levels in preterm and full-term neonates and their respective mothers, to assess their relationship with the degree of oxidative stress and the levels of vitamin C, an important antioxidant of the body. Material and methods: The studied groups included 70 neonates, 30 preterm (24-36 weeks of gestation) and 40 full-term (37-42 weeks) neonates. Blood samples were obtained from the cord blood in neonates and from the antecubital vein in their mothers at the time of delivery. Plasma susceptibility to LPO was fluorometrically measured before and after its incubation with 2,2'-azobis-2- amidinopropane hydrochloride (AAPH). Plasma vitamin C level was measured by HPLC. Results: The basal LPO levels were similar in all groups of patients. After AAPH incubation, however, plasma LPO significantly (P<0.0001) increased in all groups, although maternal plasma (full-term, 6.62±0.14 and preterm, 8.76±0.03 mmol/l) showed higher (P<0.001) levels of LPO than their respective babies (full-term, 5.11±0.03 and preterm, 7.74±0.15 mmol/l). AAPH-induced LPO was higher in both maternal and preterm neonates’ plasma than in full-term ones (P<0.001). Vitamin C levels were similar in maternal plasma of both groups, but preterm neonates showed higher levels than full-term ones (171.65±9.38 vs. 118.25±2.75 mmol/l respectively, P<0.001). Conclusions: The results suggest that the preterm group was more prone to LPO than the full-term group, whereas vitamin C was not correlated with the degree of oxidative stress.This work was partially supported by grants G03/137, PI02/1447 and PI03/0817 from Instituto de Salud Carlos III, Spain, and CTS-101 from Consejería de Educación, Junta de Andalucía, Spain

Composición de melatonina o sus derivados con coenzima q10 y su uso contra el envejecimiento de la piel

Número de publicación: ES2394245 B2 . Número de solicitud: 201231849.Composición de melatonina o sus derivados con coenzima Q10 Y su uso contra el envejecimiento de la piel. La presente invención se refiere a una composición que comprende melatonina, metabolito o derivado de la misma y coenzima Q10 Y su uso para la elaboración de una composición cosmética o farmacéutica para el tratamiento de la piel, ya que esta composición potencia la entrada de ambas moléculas en la mitocondria y facilita una absorción transdérmica, pudiendo alcanzar tanto la melatonina como la CoQ1O todos los estratos de la piel.Universidad de Granad

Agomelatine in Depressive Disorders: Its Novel Mechanisms of Action

Disruptions in sleep and sleep–wake cycle regulation have been identified as one of the main causes for the pathophysiology of depressive disorders. The search has been on for the identification of an ideal antidepressant that could improve both sleep disturbances and depressive symptomatology. Melatonin, the major hormone of the pineal gland, has been shown to improve sleep and is involved in the regulation of the sleep–wake cycle. Identification of high concentrations of MT1 and MT2 melatonergic receptors in the suprachiasmatic nucleus of the anterior hypothalamus, the structure concerned with regulation of circadian rhythms and sleep–wake cycles, has led to the development of melatonergic agonists with greater potency and longer durations of action. Agomelatine is one such melatonergic agonist that acts specifically on MT1/MT2 melatonergic receptors and at the same time exhibits 5-HT2C antagonism, a property that is utilized by current antidepressants that are in clinical use. Agomelatine has been shown to be effective in a number of animal models of depression

Relationship Between Salivary Melatonin and Severity of Periodontal Disease

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141566/1/jper1533.pd

iMS-Bmal1−/− mice show evident signs of sarcopenia that are counteracted by exercise and melatonin therapies

This study was partially supported by grants from the Instituto de Salud Carlos III through the grants PI19‐01372 and CB/10/00238 (co‐funded by European Regional Development Fund/European Social Fund “Investing in your future”); the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (CTS‐101), Spain. José Fernández‐Martínez is supported by an FPU fellowship from the Ministerio de Educación, Spain; Yolanda Ramírez‐Casas has a PFIS fellowship from the Instituto de Salud Carlos III; Paula Aranda‐Martínez has a fellowship from grant no. P18‐RT‐698, and Alba López‐Rodríguez has a fellowship from grant no. P18‐RT‐3222, from the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía.Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in Bmal1 clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible Bmal1 knockout mice (iMS-Bmal1−/−) were examined by phenotypic tests and light and electron microscopy. Our results revealed a disruption of the normal activity/rest rhythm, a drop in skeletal muscle function and mass, and increased frailty in male and female iMS-Bmal1−/− animals compared to controls. A reduction in muscle fiber size and increased collagenous tissue were also detected, accompanied by reduced mitochondrial oxidative capacity and a compensatory shift towards a more oxidative fiber type. Electron microscopy further supports mitochondrial impairment in mutant mice. Melatonin and exercise ameliorated the damage caused by loss of Bmal1 in mutant mice, except for mitochondrial damage, which was worsened by the latter. Thus, iMS-Bmal1−/− mice let us to identify Bmal1 deficiency as the responsible for the appearance of sarcopenia in the gastrocnemius muscle. Moreover, the results support the exercise and melatonin as therapeutic tools to counteract sarcopenia, by a mechanism that does not require the presence of Bmal1.Ministerio de Educación, Spain P18‐RT‐3222, P18‐RT‐698Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucíanstituto de Salud Carlos III: CB/10/00238, PI19‐01372 ISCIIIEuropean Regional Development Fund ERDFJunta de Andalucía CTS‐10

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin’s co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.Shun-Fa Yang, Grant #CHS-2016-E-002-Y2

Review Insights into the Role of Plasmatic and Exosomal microRNAs in Oxidative Stress-Related Metabolic Diseases

A common denominator of metabolic diseases, including type 2 diabetes Mellitus, dyslipidemia, and atherosclerosis, are elevated oxidative stress and chronic inflammation. These complex, multi-factorial diseases are caused by the detrimental interaction between the individual genetic background and multiple environmental stimuli. The cells, including the endothelial ones, acquire a preactivated phenotype and metabolic memory, exhibiting increased oxidative stress, inflammatory gene expression, endothelial vascular activation, and prothrombotic events, leading to vascular complications. There are different pathways involved in the pathogenesis of metabolic diseases, and increased knowledge suggests a role of the activation of the NF-kB pathway and NLRP3 inflammasome as key mediators of metabolic inflammation. Epigenetic-wide associated studies provide new insight into the role of microRNAs in the phenomenon of metabolic memory and the development consequences of vessel damage. In this review, we will focus on the microRNAs related to the control of anti-oxidative enzymes, as well as microRNAs related to the control of mitochondrial functions and inflammation. The objective is the search for new therapeutic targets to improve the functioning of mitochondria and reduce oxidative stress and inflammation, despite the acquired metabolic memoryCIBER-Consorcio Centro de Investigación Biomédica en Red-(CB16/10/00238Instituto de Salud Carlos III, Ministerio de Ciencia e InnovaciónGrant of the FUNDACIÓN EUGENIO RODRIGUEZ PASCUAL (ERP-2021),Call 2021, Spai

Role of c-miR-21, c-miR-126, Redox Status, and Inflammatory Conditions as Potential Predictors of Vascular Damage in T2DM Patients

The development of type 2 diabetes mellitus (T2DM) vascular complications (VCs) is associated with oxidative stress and chronic inflammation and can result in endothelial dysfunctions. Circulating microRNAs play an important role in epigenetic regulation of the etiology of T2DM. We studied 30 healthy volunteers, 26 T2DM patients with no complications, and 26 T2DM patients with VCs, to look for new biomarkers indicating a risk of developing VCs in T2DM patients. Peripheral blood samples were used to determine redox state, by measuring the endogenous antioxidant defense system (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GRd; glutathione peroxidase, GPx; and glucose-6-phosphate dehydrogenase, G6DP) and markers of oxidative damage (advanced oxidation protein products, AOPP; lipid peroxidation, LPO). Additionally, inflammatory marker levels (IL-1, IL-6, IL-18, and TNF- ), c-miR-21, and c-miR-126 expression were analyzed. T2DM patients showed the highest oxidative damage with increased GSSG/GSH ratios, LPO, and AOPP levels. In both diabetic groups, we found that diminished SOD activity was accompanied by increased CAT and decreased GRd and G6PD activities. Diabetic patients presented with increased relative expression of c-miR-21 and decreased relative expression of c-miR-126. Overall, c-miR-21, SOD, CAT, and IL-6 had high predictive values for diabetes diagnoses. Finally, our data demonstrated that IL-6 exhibited predictive value for VC development in the studied population. Moreover, c-miR- 21 and c-miR-126, along with GPx and AOPP levels, should be considered possible markers for VC development in future studies.University of GranadaEugenio Rodriguez Pascual Foundation ERP-2021CIBERfes (ISCIII, Spain) CB16-10-0023

The Role of Mitochondria in Brain Aging and the Effects of Melatonin

Melatonin is an endogenous indoleamine present in different tissues, cellular compartments and organelles including mitochondria. When melatonin is administered orally, it is readily available to the brain where it counteracts different processes that occur during aging and age-related neurodegenerative disorders. These aging processes include oxidative stress and oxidative damage, chronic and acute inflammation, mitochondrial dysfunction and loss of neural regeneration. This review summarizes age related changes in the brain and the importance of oxidative/nitrosative stress and mitochondrial dysfunction in brain aging. The data and mechanisms of action of melatonin in relation to aging of the brain are reviewed as well