Dietary interventions for fetal growth restriction – therapeutic potential of dietary nitrate supplementation in pregnancy

Abstract

Fetal growth restriction (FGR) affects around 5% of pregnancies and is associated with significant short- and long-term adverse outcomes. A number of factors can increase the risk of FGR, one of which is poor maternal diet. In terms of pathology, both clinically and in many experimental models of FGR, impaired uteroplacental vascular function is implicated, leading to a reduction in the delivery of oxygen and nutrients to the developing fetus. Whilst mechanisms underpinning impaired uteroplacental vascular function are not fully understood, interventions aimed at enhancing nitric oxide (NO) bioavailability remain a key area of interest in obstetric research. In addition to endogenous NO production from the amino acid L-arginine, via nitric oxide synthase (NOS) enzymes, research in recent years has established that significant NO can be derived from dietary nitrate, via the 'alternative NO pathway'. Dietary nitrate, abundant in green leafy vegetables and beetroot, can increase NO bioactivity, conferring beneficial effects on cardiovascular function and blood flow. Given the beneficial effects of dietary nitrate supplementation to date in non-pregnant humans and animals, current investigations aim to assess the therapeutic potential of this approach in pregnancy to enhance NO bioactivity, improve uteroplacental vascular function and increase fetal growth.

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Oropharyngeal swabs analyzed by ddPCR is a quantitative, rapid, and effective method for minimally invasive oncogenic HPV detection. This assay represents the most sensitive and accurate mode of HPV detection in OPSCC without a tissue biopsy in the available literature.

http://sfaki.blogspot.com/2017/01/hpv-opscc-is-commonly-diagnosed-by-rt.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Tumor uptake of 18F-BPA and 11C-Met : The distribution of 4-borono-2-18F-fluoro-phenylalanine (18F-BPA) and L-[methyl-11C] methionine (11C-Met) in normal organs and tumors and to evaluate the usefulness of 11C-Met/PET in screening potential candidates for boron neutron capture therapy (BNCT).

http://sfaki.blogspot.com/2017/01/relationship-between-uptake-of-18f.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

A novel homozygous truncating mutation of the SFRP4 gene in Pyle's disease

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Diltiazem prevents stress-induced contractile deficits in cardiomyocytes, but does not reverse the cardiomyopathy phenotype in Mybpc3-knock-in mice

Abstract

Left ventricular hypertrophy, diastolic dysfunction and fibrosis are main features of hypertrophic cardiomyopathy (HCM). Guidelines recommend β-adrenoceptor or Ca²⁺ channel antagonists as pharmacological treatment. The Ca²⁺ channel blocker diltiazem recently showed promising beneficial effects in pre-clinical HCM, particularly in patients carrying MYBPC3 mutations. In the present study we evaluated whether diltiazem could ameliorate or reverse the disease phenotype in cells and in vivo in Mybpc3-targeted knock-in (KI) mouse model of HCM. Sarcomere shortening and Ca²⁺ transient were measured in KI and wild-type (WT) cardiomyocytes in basal condition (1-Hz pacing) and under stress conditions (30 nm isoprenaline, 5-Hz pacing) with or without pre-treatment with 1 μm diltiazem. KI cardiomyocytes exhibited lower diastolic sarcomere length (dSL) at baseline, a tendency to a higher positive inotropic response to isoprenaline than WT, and a marked reduction of dSL and a tendency towards arrhythmias under stress conditions. Pre-treatment of cardiomyocytes with 1 μm diltiazem reduced the drop in dSL and arrhythmia frequency in KI, and attenuated the positive inotropic effect of isoprenaline. Furthermore, diltiazem reduced the contraction amplitude at 5 Hz but did not affect diastolic Ca²⁺ load and Ca²⁺ transient amplitude. Six-month diltiazem treatment of KI mice did not reverse cardiac hypertrophy and dysfunction, activation of the fetal gene program or fibrosis. In conclusion, diltiazem blunted the response to isoprenaline in WT and KI and improved diastolic relaxation under stress conditions in KI cardiomyocytes. This beneficial effect of diltiazem in cells did not translate in therapeutic efficacy when applied chronically in KI mice.

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Late gestational intermittent hypoxia induces metabolic and epigenetic changes in male adult offspring mice

Abstract

Pregnancy, particularly late gestation, has been associated with a relatively high prevalence of obstructive sleep apnea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis, and metabolic function in offspring. We hypothesized that IH during late pregnancy (LG-IH) may increase the propensity for metabolic dysregulation and obesity in adult offspring via epigenetic modifications. Time-pregnant female C57BL/6 mice were exposed to LG-IH or room air (LG-RA) during days 13–18 of gestation. At 24 weeks, blood samples were collected from offspring mice for lipid profiles and insulin resistance (HOMA-IR), indirect calorimetry was performed, and visceral white adipose tissues (VWAT) were assessed for inflammatory cells as well as for differentially methylated gene regions (DMR) using MeDIP-Chip. Body weight, food intake, adiposity index, fasting insulin, triglycerides, and cholesterol levels were all significantly higher in LG-IH male but not female offspring. LG-IH also altered metabolic expenditure and locomotor activities in male offspring, and increased number of pro-inflammatory macrophages emerged in VWAT along with 1520 DMRs (P < 0.0001), associated with 693 genes. Pathway analyses showed that genes affected by LG-IH were mainly associated with molecular processes related to metabolic regulation and inflammation. LG-IH induces metabolic dysfunction as reflected by increased body weight and adiposity index in adult male offspring that is paralleled by epigenomic alterations and inflammation in VWAT. Thus, perturbations to fetal environment by OSA during pregnancy can therefore have long-term detrimental effects to the fetus, and lead to persistent metabolic dysfunction in adulthood.

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Tensions flare over Calif. ambulance response to calls

The firefighters union claimed ambulances from AMR are frequently unavailable to cover their response area

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Can't intubate can't ventilate, use a small size Air-Q and the Pudgy-Baby maneuver

The incidence of difficult mask ventilation and difficult tracheal intubation is higher in obese and obstructive sleep apnea (OSA) patients [1]. When a "cannot intubate cannot ventilate" (CICV) situation is encountered, a supraglottic airway device (SAD) should be inserted to rescue ventilation. Unfortunately, failure to achieve adequate ventilation with a SAD is also common in obese and OSA patients [2] which may lead to a catastrophic outcome if a surgical airway is not immediately established.

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Acute renal injury in the course of a large pleural effusion

Furst B. and colleagues described in this journal [1] an abrupt hemodynamic decompensation after performing pericardial window in a patient with malignant pericardial effusion (PRE). The hemodynamic consequences promptly reversed when a concurrent large pleural effusion (PLE) was evacuated.

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The sedative effects of the intranasal administration of dexmedetomidine in children undergoing surgeries compared to other sedation methods: A systematic review and meta-analysis

Administration of intranasal dexmedetomidine for sedation is comfortable and effective in children who are afraid of needles, and it offers efficient sedation similar to that of intravenous administration. We performed a systematic review and meta-analysis to evaluate the clinical effects of the pre-procedural administration of intranasal dexmedetomidine.

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Diverse role of Survival Motor Neuron Protein

Publication date: Available online 15 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Ravindra N. Singh, Matthew D. Howell, Eric W. Ottesen, Natalia N. Singh
The multifunctional Survival Motor Neuron (SMN) protein is required for the survival of all organisms of the animal kingdom. SMN impacts various aspects of RNA metabolism through the formation and/or interaction with ribonucleoprotein (RNP) complexes. SMN regulates biogenesis of small nuclear RNPs, small nucleolar RNPs, small Cajal body-associated RNPs, signal recognition particles and telomerase. SMN also plays an important role in DNA repair, transcription, pre-mRNA splicing, histone mRNA processing, translation, selenoprotein synthesis, macromolecular trafficking, stress granule formation, cell signaling and cytoskeleton maintenance. The tissue-specific requirement of SMN is dictated by the variety and the abundance of its interacting partners. Reduced expression of SMN causes spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. SMA displays a broad spectrum ranging from embryonic lethality to an adult onset. Aberrant expression and/or localization of SMN has also been associated with male infertility, inclusion body myositis, amyotrophic lateral sclerosis and osteoarthritis. This review provides a summary of various SMN functions with implications to a better understanding of SMA and other pathological conditions.



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Effects of beta-hydroxy-beta-methylbutyrate (HMB) on the expression of ubiquitin ligases, protein synthesis pathways and contractile function in extensor digitorum longus (EDL) of fed and fasting rats

Abstract

Beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, enhances the gain of skeletal muscle mass by increasing protein synthesis or attenuating protein degradation or both. The aims of this study were to investigate the effect of HMB on molecular factors controlling skeletal muscle protein synthesis and degradation, as well as muscle contractile function, in fed and fasted conditions. Wistar rats were supplied daily with HMB (320 mg/kg body weight diluted in NaCl-0.9%) or vehicle only (control) by gavage for 28 days. After this period, some of the animals were subjected to a 24-h fasting, while others remained in the fed condition. The EDL muscle was then removed, weighed and used to evaluate the genes and proteins involved in protein synthesis (AKT/4E-BP1/S6) and degradation (Fbxo32 and Trim63). A sub-set of rats were used to measure in vivo muscle contractile function. HMB supplementation increased AKT phosphorylation during fasting (three-fold). In the fed condition, no differences were detected in atrogenes expression between control and HMB supplemented group; however, HMB supplementation did attenuate the fasting-induced increase in their expression levels. Fasting animals receiving HMB showed improved sustained tetanic contraction times (one-fold) and an increased muscle to tibia length ratio (1.3-fold), without any cross-sectional area changes. These results suggest that HMB supplementation under fasting conditions increases AKT phosphorylation and attenuates the increased of atrogenes expression, followed by a functional improvement and gain of skeletal muscle weight, suggesting that HMB protects skeletal muscle against the deleterious effects of fasting.

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Time-course investigation of blood–brain barrier permeability and tight junction protein changes in a rat model of permanent focal ischemia

Abstract

Permanent middle cerebral artery occlusion (pMCAO) is an animal model that is widely used to simulate human ischemic stroke. However, the timing of the changes in the expression of tight junction (TJ) proteins and synaptic proteins associated with pMCAO remain incompletely understood. Therefore, to further explore the characteristics and mechanisms of blood–brain barrier (BBB) damage during cerebral ischemic stroke, we used a pMCAO rat model to define dynamic changes in BBB permeability within 120 h after ischemia in order to examine the expression levels of the TJ proteins claudin-5 and occludin and the synaptic proteins synaptophysin (SYP) and postsynaptic density protein 95 (PSD95). In our study, Evans blue content began to increase at 4 h and was highest at 8 and 120 h after ischemia. TTC staining showed that cerebral infarction was observed at 4 h and that the percentage of infarct volume increased with time after ischemia. The expression levels of claudin-5 and occludin began to decline at 1 h and were lowest at 8 and 120 h after ischemia. The expression levels of SYP and PSD95 decreased from 12 to 120 h after ischemia. GFAP, an astrocyte marker, gradually increased in the cortex penumbra over time post-ischemia. Our study helps clarify the characteristics of pMCAO models and provides evidence supporting the translational potential of animal stroke models.

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Sphingosine-1-phosphate pretreatment amends hypoxia-induced metabolic dysfunction and impairment of myogenic potential in differentiating C2C12 myoblasts by stimulating viability, calcium homeostasis and energy generation

Abstract

Sphingosine-1-phosphate (S1P) has a role in transpiration in patho-physiological signaling in skeletal muscles. The present study evaluated the pre-conditioning efficacy of S1P in facilitating differentiation of C2C12 myoblasts under a normoxic/hypoxic cell culture environment. Under normoxia, exogenous S1P significantly promoted C2C12 differentiation as evident from morphometric descriptors and differentiation markers of the mature myotubes, but it could facilitate only partial recovery from hypoxia-induced compromised differentiation. Pretreatment of S1P optimized the myokine secretion, intracellular calcium release and energy generation by boosting the aerobic/anaerobic metabolism and mitochondrial mass. In the hypoxia-exposed cells, there was derangement of the S1PR_1–3 expression patterns, while the same could be largely restored with S1P pretreatment. This is being proposed as a plausible underlying mechanism for the observed pro-myogenic efficacy of exogenous S1P preconditioning. The present findings are an invaluable addition to the existing knowledge on the pro-myogenic potential of S1P and may prove beneficial in the field of hypoxia-related myo-pathologies.

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Inhibition of ghrelin-induced feeding in rats by pretreatment with a novel dual orexin receptor antagonist

Abstract

Orexin-A and -B, and ghrelin are potent orexigenic peptides. The effects of ACT462206, a novel dual orexin receptor antagonist (DORA), on ghrelin-induced feeding were examined in adult male Wistar rats. Hyperphagia induced by the intracerebroventricular (icv) administration of ghrelin was significantly suppressed for at least 2 h by pretreatment with icv administration of DORA. A marked increase was observed in the number of neurons showing Fos immunoreactivity in the paraventricular nucleus, arcuate nucleus and lateral hypothalamic area (LHA), 90 min after icv administration of ghrelin. Pretreatment with DORA significantly decreased the number of Fos-immunoreactive (IR) neurons; however, Fos immunoreactivity remained significantly increased. Double-immunostaining for Fos and orexin-A showed that many orexin-A-IR neurons in the LHA coexisted with Fos immunoreactivity after icv administration of ghrelin, but their number was reduced significantly by DORA pretreatment. These results suggest that centrally administered ghrelin may activate the orexinergic and non-orexinergic pathways responsible for the regulation of feeding.

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Modeling Depression in Animals: Behavior as the Basis for the Methodology, Assessment Criteria, and Classification

This review analyzes current progress in the modeling of depressive disorders in animals. The criteria and classification systems for existing models are considered, as are approaches to assessing the validity of models. Despite the use of numerous approaches to modeling depressive states, based not only on impairments to the motivational mechanisms of the brain, but also on impairments to the emotional mechanisms, no satisfactory model creating a stable depressive state has yet been developed. Nonetheless, the diversity of existing models is undoubtedly positive, as it provides for targeted studies of individual neurobiological mechanisms and patterns of development of depressive states in humans, as well as studies of the mechanisms of action and predictions of the pharmacological profiles of potential drugs for the treatment of depression.

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Development of Morphological Studies on the Actions of Gravitational Overloading on the Body at the Kirov Military Medical Academy

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Efficacy and Safety of the Use of Baclofen in the Treatment of Alcohol Dependent (a Double-Blind, Randomized, Placebo-Controlled Pilot Study)

Objective. To study the efficacy and use of baclofen (Baclosan) for stabilizing remission in patients with alcoholism. Materials and methods. A total of 32 patients with alcoholism were randomized to two groups. Patients of group 1 (16 patients) received baclofen (50 mg/day) for three months; patients of group 2 received a placebo of identical appearance. All patients were required to attend the clinic every week for monitoring of remission (alcohol consumption) and assessment of the levels of alcohol attraction (craving), affective disorders (depression and anxiety), and γ-glutamyltransferase (GGT) activity, and for monitoring of compliance with medication (urine riboflavin). Alcohol consumption was monitored by retrospective analysis and assay of GGT. Anxiety was evaluated using the Hamilton and Spielberger scales. Depression was assessed on the Montgomery-Asberg Depression Scale. Alcohol cravings were assessed using obsessive-compulsive, Pennsylvania, and visual analog scales. Overall assessment of treatment efficacy was obtained using the Clinical Global Impression scale. The study followed a double-blind design. Results and conclusions. No significant difference in measures of the efficacy of stabilizing remission was seen between the baclofen and placebo groups in patients with alcoholism (probably due to insufficiently large cohort sizes). Measures of holding patients in remission and of alcohol consumption in the baclofen group were somewhat better than in the placebo group; between-group differences in these measures approached statistical significance, pointing to a greater efficacy for baclofen than placebo in alcoholism. Baclofen did not show any significant difference from placebo in terms of the number of side effects (adverse events) and effects on liver enzyme activity, which is evidence for its good tolerance and safety in this contingent of patients. The authors take the view that evidence-based conclusions regarding The efficacy of baclofen in the treatment of alcoholism require further studies in patients using larger cohorts.

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Cell Contact Protein β-Catenin in Ependymal and Epithelial Cells in the Choroid Plexus of the Lateral Ventricles of the Brain

The aim of the present work was to study the distribution of cell contact protein β-catenin in the choroid plexus and ependyma of the lateral ventricles of the brain. Experiments were performed using frontal sections of brains from Wistar rats (n = 10) using polyclonal antibodies to β-catenin. Preparations were analyzed under the microscope in transmitted light and by confocal laser microscopy. The distribution of β-catenin in different projections was studied by three-dimensional reconstruction. The results identified differences in the distributions of this protein in the ependyma and choroid plexus. In contrast to the ependyma, β-catenin is distributed in choroid plexus cells in the same way as in monolayer epithelial tissues (at the basal and lateral margins of the cells). This may be evidence that the ependyma and epithelium of the choroid plexus are of different tissue types, despite their common origin.

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Optimization of Antidepressant Therapy in Conditions of the Gerontology Psychiatric Out-Patient Clinic

Objective. To carry out a comparative assessment of the efficacy and safety of monotherapy with a new-generation antidepressant (venlafaxin, agomelatine, or fluvoxamine) and complex antidepressant therapy using one of these antidepressants in combination with acetyl-L-carnitine (ALC, Carnicetin) for the treatment of depression in elderly patients in a gerontology psychiatric out-patients clinic. Materials and methods. Two groups of patients (aged 60–79 years) with mild or moderate depression, comparable in terms of the main demographic and clinical characteristics, received antidepressant mono- or complex (antidepressant and ALC) therapy for eight weeks. Results. The use of complex therapy including the neuroprotector Carnicetin, which has neurotrophic and energotropic mechanisms of action, was found to provide a faster-onset therapeutic response and a stronger effect than antidepressant monotherapy, which was supported by a significant reduction in depressive disorders, including measures of the severity of anxiety, along with improvements in the patients' cognitive functioning. Use of complex therapy was accompanied by a decrease in the frequency of adverse events. Conclusions. The results obtained here allow inclusion of Carnicetin into the complex antidepressant treatment to be recommended for use in gerontology psychiatric out-patient clinics.

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Dynamics of Blood Cytokine Concentrations in Rats with Different Behavioral Characteristics after Acute Stress

Changes in peripheral blood cytokine contents in behaviorally passive and active Wistar rats were assessed at different time points after acute stressing using a restraint model during the dark part of the day. In passive animals, decreases in the concentrations of most of the pro- and anti-inflammatory cytokines studied were most marked immediately and particularly three days after stress. Changes in the cytokine profile of the blood following experimental stress were less marked in behaviorally active individuals: significant decreases from normal were seen only for the proinflammatory cytokine IL-1α and the anti-inflammatory cytokines IL-4 and IL-13. In contrast to passive rats, these changes were more marked in active individuals one day after negative emotional loading. These data illustrate the specific features of the involvement of immunoactive substances in the system controlling the physiological functions and forming individual resistance to the negative sequelae of stress.

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Functional Organization of the Cerebral Cortex in Cued and Implicit Modality-Specific Anticipatory Attention. Analysis of α-Rhythm Coherence in the Sources Space

Studies in healthy right-handed subjects (N = 16, mean age 23 ± 5.7 years) analyzed the functional organization of the cerebral cortex during preparation to solve visual and auditory sensory tasks in two conditions: (1) anticipation of a visual or auditory signal after being told its modality (cued anticipatory attention) and (2) implicit anticipation formed during multiple repetition of a given sequence of visual and auditory stimuli. In both conditions subjects had to perform the same task – to identify the order of the stimuli (visual or auditory) in monomodal pairs. During the prestimulus period, the α frequency range was used to assess the coherence of cortical sources corresponding to previously selected cortical regions (regions of interest). More functional connections between cortical zones in the frontoparietal modulatory system were seen in cued anticipatory attention than during the period preceding appearance of the prompt stimulus, this obtaining in both sensory tasks. There was also a greater number of local connections between sensory-specific and associative (parietal and prefrontal) areas. Implicit anticipation preceding execution of the visual task was accompanied by an increase in connections between the ventral premotor cortex and the caudal (parietal and occipital) areas of the right hemisphere. Execution of the auditory task was preceded by an increase in connections between the auditory sensory cortex, the rostral part of the supplementary motor area, and the ventral premotor area. In contrast to cued attention, implicit anticipation was not accompanied by changes in frontoparietal connections. These results provide evidence of significant differences in the cerebral organization of these two types of anticipatory attention.

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Functional Activity of the Insulin Signaling System of the Brain in Health and Type 2 Diabetes Mellitus

The insulin signal system of the brain plays a key role in regulating fundamental cellular process in neurons, and it controls metabolic processes in the CNS and the periphery. In hypothalamic neurons, the insulin signaling system interacts closely with other signal systems controlled by leptin, melanocortin peptides, dopamine, and serotonin, and is a key component of the signal network of the hypothalamus, integrating and transforming central and peripheral signals. Impairments to the insulin system of the brain lead to the development of central insulin resistance, which is one of the prime causes of type 2 diabetes mellitus (DM), metabolic syndrome, and Alzheimer's disease. Timely restoration of the insulin system of the brain is an effective approach for the prophylaxis and treatment of type 2 DM and associated neurodegenerative diseases. This review analyzes and assesses published data and our own results on the structural-functional organization of the insulin signal system of the brain, impairments to insulin signaling in the CNS, and approaches to its restoration in type 2 DM.

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Deciphering the molecular mechanisms involved in HIV-associated lipoatrophy by transcriptomics: a pilot study

Abstract

HIV-associated lipoatrophy (LA) has considerable implications for risk of metabolic diseases, quality of life, and adherence to treatments. Although it has decreased in high-income countries, it is still very common in resource-limited countries. Understanding the pathophysiological mechanisms of LA can open the possibility to explore new ways to treat or prevent this condition. To identify new markers for an accurate and quick diagnosis will be also of interest. Thus, we aimed to examine functional classes of genes implicated in LA and to identify potential new markers for an accurate/quick diagnosis of LA and future complications. Eighteen participants were recruited: seven healthy volunteers, five non-LA-HIV patients, and six LA-HIV subjects. Clinical lipoatrophy was considered when changes in fat volume in the cheeks next to the nose, lateral aspect of the face, legs, arms, and buttocks were observed by the physicians. mRNA was isolated from peripheral blood mononuclear cells (PBMCs) to perform a transcriptomic and Gene Ontology analysis. To confirm RNA sequencing results, qPCRs were developed. A total of 55 genes were differentially expressed between LA and non-LA patients. Thirty-seven genes were overexpressed, whereas 18 genes were repressed. Functional analysis showed that overexpressed genes were involved in lymphocyte/neutrophil activation, inflammation, and atherogenesis. Several lymphoma markers and members of the lipocalin and aquaporin families were also found more expressed in LA patients. In contrast, most of the genes found less expressed in LA subjects were involved in angiogenesis and protection against myocardial infarction. Our results demonstrated a distinct transcriptomic signature in PBMCs of LA patients in comparison with non-LA-HIV subjects and, therefore, provided novel insights to the pathogenesis of HIV-associated lipoatrophy. Our study also highlights the potential usage of some of these genes as early markers of future complications.

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Ideal cardiovascular health and liver enzyme levels in European adolescents; the HELENA study

Abstract

There is an increasing interest for the role of liver enzymes as predictors of non-liver-related morbidity and mortality. The American Heart Association (AHA) described the ideal cardiovascular health concept as a score of seven cardiovascular health behaviors and factors that can be used to monitor and predict ideal cardiovascular health over time. This study aimed to examine the association of the ideal cardiovascular health (ICH), as defined by the AHA, with liver enzyme levels in European adolescents. A total of 637 adolescents (54.6% females), aged 14.6 ± 1.2 years from nine European countries participated in this cross-sectional study. Blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase were measured and the AST/ALT ratio calculated. Ideal cardiovascular health was defined as meeting ideal levels of the following components: four behaviors (smoking, body mass index, physical activity, and diet) and three factors (total cholesterol, blood pressure, and glucose). A higher number of ideal cardiovascular health behaviors, factors, and ideal cardiovascular health index were associated with lower ALT (P < 0.05, P < 0.001, and P < 0.001, respectively) and gamma-glutamyltransferase (P < 0.001, P < 0.01, and P < 0.001, respectively) levels. Similarly, a higher number of ideal cardiovascular health behaviors (P < 0.01), factors (P < 0.01), and ideal cardiovascular health index (P < 0.001) were associated with a higher aspartate aminotransferase to alanine aminotransferase ratio. These findings reinforce the usefulness of the ICH index as an instrument to identify target individuals and promote cardiovascular health in adolescents, and it also extends these observations to the liver manifestation of the metabolic syndrome.

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Sexual dimorphism in obesity-related genes in the epicardial fat during aging

Abstract

Aging increases the risk of cardiovascular disease and metabolic syndrome. Alterations in epicardial fat play an important pathophysiological role in coronary artery disease and hypertension. We investigated the impact of normal aging on obesity-related genes in epicardial fat. Sex-specific changes in obesity-related genes with aging in epicardial fat (EF) were determined in young (6 months) and old (30/36 months) female and male, Fischer 344 × Brown Norway hybrid (FBN) rats, using a rat obesity RT² PCR Array. Circulating sex hormone levels, body and heart weights were determined. Statistical significance was determined using two-tailed Student's t test and Pearson's correlation. Our results revealed sex-specific differences in obesity-related genes with aging. Dramatic changes in the expression profile of obesity-related genes in EF with aging in female, but not in male, FBN rats were observed. The older (30 months) female rats had more significant variations in the abundance of obesity-related genes in the EF compared to that seen in younger female rats or both age groups in male rats. A correlation of changes in obesity-related genes in EF to heart weights was observed in female rats, but not in male rats with aging. No correlation was observed to circulating sex hormone levels. Our findings indicate a dysfunctional EF in female rats with aging compared to male rats. These findings, with further functional validation, might help explain the sex differences in cardiovascular risk and mortality associated with aging observed in humans.

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