Mammalian aquaglyceroporin function in metabolism

AbstractAquaglyceroporins are integral membrane proteins that are permeable to glycerol as well as water. The movement of glycerol from a tissue/organ to the plasma and vice versa requires the presence of different aquaglyceroporins that can regulate the entrance or the exit of glycerol across the plasma membrane. Actually, different aquaglyceroporins have been discovered in the adipose tissue, small intestine, liver, kidney, heart, skeletal muscle, endocrine pancreas and capillary endothelium, and their differential expression could be related to obesity and the type 2 diabetes.Here we describe the expression and function of different aquaglyceroporins in physiological condition and in obesity and type 2 diabetes, suggesting they are potential therapeutic targets for metabolic disorders

Epigenetic Switch at Atp2a2 and Myh7 Gene Promoters in Pressure Overload-Induced Heart Failure

Re-induction of fetal genes and/or re-expression of postnatal genes represent hallmarks of pathological cardiac remodeling, and are considered important in the progression of the normal heart towards heart failure (HF). Whether epigenetic modifications are involved in these processes is currently under investigation. Here we hypothesized that histone chromatin modifications may underlie changes in the gene expression program during pressure overload-induced HF. We evaluated chromatin marks at the promoter regions of the sarcoplasmic reticulum Ca2+ATPase (SERCA-2A) and β-myosin-heavy chain (β-MHC) genes (Atp2a2 and Myh7, respectively) in murine hearts after one or eight weeks of pressure overload induced by transverse aortic constriction (TAC). As expected, all TAC hearts displayed a significant reduction in SERCA-2A and a significant induction of β-MHC mRNA levels. Interestingly, opposite histone H3 modifications were identified in the promoter regions of these genes after TAC, including H3 dimethylation (me2) at lysine (K) 4 (H3K4me2) and K9 (H3K9me2), H3 trimethylation (me3) at K27 (H3K27me3) and dimethylation (me2) at K36 (H3K36me2). Consistently, a significant reduction of lysine-specific demethylase KDM2A could be found after eight weeks of TAC at the Atp2a2 promoter. Moreover, opposite changes in the recruitment of DNA methylation machinery components (DNA methyltransferases DNMT1 and DNMT3b, and methyl CpG binding protein 2 MeCp2) were found at the Atp2a2 or Myh7 promoters after TAC. Taken together, these results suggest that epigenetic modifications may underlie gene expression reprogramming in the adult murine heart under conditions of pressure overload, and might be involved in the progression of the normal heart towards HF

Physical activity in the prevention of peripheral artery disease in the elderly

Aging is a well-known cardiovascular risk factor and cardiovascular diseases (CVD) are estimated to be the most common cause of death in the elderly. Peripheral arterial disease (PAD) represents an important clinical manifestation of CVD leading to increase morbidity and mortality, especially in elderly population. The correct management of PAD population includes the prevention of cardiovascular events and relief of symptoms, most commonly intermittent claudication. Progressive physical activity is an effective treatment to improve walking distance and to reduce mortality and cardiovascular events in patients with PAD, however the ability to effectively engage in physical activity often declines with increasing age. The maintenance and increase of reserve functional capacity are important concepts in the elderly population. Ultimately, the goal in participation of physical activity in the healthy elderly population is maintenance and development of physical functional reserve capacity. Therefore, for individuals suffering of PAD, appropriate physical activity in the form of supervised exercise may serve as a primary therapy. Although there are few direct comparisons of therapeutic exercise programs vs. pharmacological or surgical interventions, these increases in walking distance are greater than those reported for the most widely used agents for claudication, pentoxyphylline, and cilostazol. Despite a reduction in mortality and improvement of quality of life caused by physical activity in the PAD population, the molecular, cellular, and functional changes that occur during physical activity are not completely understood. Therefore, this review article aims at presenting an overview of recent established clinical and molecular findings addressing the role of physical activity on PAD in the older population

Transradial approach for the endovascular treatment of type I endoleak after aortic aneurysm repair: a case report

Endovascular repair of aortic aneurysms (EVAR) is obtained through the positioning of an aortic stent-graft, which excludes the aneurysmatic dilation. Type I endoleak is the most common complication, and it is caused by an incompetent proximal or distal attachment site, causing the separation between the stent-graft and the native arterial wall, and in turn creating direct communication between the aneurysm sac and the systemic arterial circulation. Endoleak occurrence is associated with high intrasac pressures, and requires a quick repair to prevent abdominal aortic aneurysm rupture

Providing a nurse-led complex nursing INtervention FOcused on quality of life assessment on advanced cancer patients: The INFO-QoL pilot trial.

PURPOSE Unmet needs for advanced-disease cancer patients are fatigue, pain, and emotional support. Little information is available about the feasibility of interventions focused on patient-reported outcome measurement developed according to the Medical Research Council (MRC) Framework in advanced-disease cancer patients. We aimed to pilot a nurse-led complex intervention focused on QoL assessment in advanced-disease cancer patients. METHODS The INFO-QoL study was based on an exploratory, nonequivalent comparison group, pre-test-post-test design. Study sites received either the INFO-QoL intervention or usual care. Adult advanced-disease cancer patients admitted to hospice inpatient units that gave their informed consent were included in the study. Subjects were 187 patients and their families and 19 healthcare professionals. We evaluated feasibility, acceptability, and patients' outcomes using the Integrated Palliative Care Outcome Scale. RESULTS Nineteen healthcare professionals were included. The mean competence score increased significantly over time (p < 0.001) and the mean usefulness score was high 8.63 (±1.36). In the post-test phase, 54 patients were allocated to the experimental unit and 36 in the comparison unit. Compared to the comparison unit, in the experimental unit anxiety (R2 = 0.07; 95% CI = -0.06; 0.19), family anxiety (R2 = 0.22; 95% CI = -0.03; 0.41), depression (R2 = 0.31; 95% CI = -0.05; 0.56) and sharing feelings (R2 = 0.09; 95% CI = -0.05; 0.23), were improved between pre-test and post-test phase. CONCLUSIONS The INFO-QoL was feasible and potentially improved psychological outcomes. Despite the high attrition rate, the INFO-QoL improved the quality and safety culture for patients in palliative care settings

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69&nbsp;%. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24&nbsp;h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3&nbsp;days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30&nbsp;min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015

AQUAGLYCEROPORINS AND ADIPOSE TISSUE

Introduction: Glycerol metabolism in normal condition and in metabolic disorders like type-2 diabetes and obesity could depend at least in part on the transmembrane transport mechanisms of glycerol. Aquaglyceroporins (AQPs) are integral membrane proteins belonging to the water channel protein family (aquaporins) that are permeable to glycerol as well as water. Adipose tissue, the main source of plasma glycerol, expresses high levels of AQP7, the first identified glycerol channel considered the sole AQP of this tissue for a decade. Different studies using AQP7-KO mice models showed contrasting results about the possible onset of obesity in adulthood. Moreover, human subjects homozygous G264V mutant, encoding for a not functional protein, did not show obesity or type 2 diabetes. Some questions arise: 1) the localization of AQP7, 2) the presence of other glycerol channels and 3) the functional role of AQPs in glycerol handling in normal condition and the impact of altered AQPs expression in metabolic syndrome. To this purpose we investigated the questions 1) and 2). Materials and Methods: Realtime RT-PCR, immunoblotting and immunofluorescence were utilized to study the expression and localization of different AQPs in human subcutaneous adipose tissue. Human cultured adipocytes were used to confirm the presence of AQP10 and the possible regulatory role of insulin and isoproterenol on AQP7 and AQP10. Finally, the water and glycerol permeability was measured by a stopped-flow light scattering method both in cultured adipocytes and in adipose plasma membrane vesicles; also the functional effect of AQP10 silencing was investigated. Results and Discussion: AQP7 and AQP10 were expressed in the white adipose tissue and localized both to the plasma membrane and to a thin rim of cytoplasm of the adipocytes. AQP7, but not AQP10, was localized also in the adipose endothelial cells. Cultured adipocytes showed that AQP7 and AQP10 labelling is mainly in the cytoplasm and in the lipid droplets with insulin reinforcing the lipid droplets staining and isoproterenol inducing its translocation to the plasma membrane. Water and glycerol permeability measurements confirmed the presence of functioning AQPs and that AQP10 knocked down adipocytes resulted in a 50% glycerol and water permeability reduction. Conclusions: These results and other recently described by the literature seem support the existence in adipose tissue of different AQPs that under hormonal control and in pathological conditions can modify their expression levels and cellular localization, suggesting them as potential therapeutic targets in obesity and metabolic syndrome

Impaired aquaporins expression in the gastrointestinal tract of rat after mercury exposure

The main route of exposure to mercury in humans is through the diet. Consequently, the gastrointestinal mucosa is exposed to the mercurial forms, where they cause intestinal fluid accumulation, mucosal injuries and diarrhea. The relationship between inorganic mercury (HgCl2 ) and methylmercury (CH3 HgCl) exposure and water movement in the gastrointestinal tract is still unexplored. The leading role of aquaporins (AQPs) in the rapid bidirectional movement of fluid in the gastrointestinal tract of mammals is well established. The present study evaluates the effect of HgCl2 and CH3 HgCl exposure on AQP expression in different portions of the gastrointestinal tract of rats treated by gavage (5 mg kg(-1) of mercury species, single dose, 4 days). The results show that mercury species reduce mRNA and protein levels of AQPs in different parts of the gastrointestinal tract. In the stomach, treated rats show a significant reduction of expression of AQP3 (80-90% for mRNA and 50% for protein) and AQP4 (95-99% for mRNA and 20-40% for protein). In the small and large intestine, treated rats experience a significant reduction of AQP3 and AQP7 expression. Protein contents of both AQPs are reduced in similar proportions in jejunum (AQP3: 40-50%; AQP7: 45-50%) and colon (AQP3: 35-40%; AQP7: 45-60%), regardless of the treatment. Our results indicate that some AQPs are downregulated in the rat gastrointestinal tract by mercury exposure, suggesting a possible role of AQPs in the development of mercury gastrointestinal symptoms