Fructose Modulates Cardiomyocyte Excitation-Contraction Coupling and Ca2+ Handling In Vitro

BACKGROUND: High dietary fructose has structural and metabolic cardiac impact, but the potential for fructose to exert direct myocardial action is uncertain. Cardiomyocyte functional responsiveness to fructose, and capacity to transport fructose has not been previously demonstrated. OBJECTIVE: The aim of the present study was to seek evidence of fructose-induced modulation of cardiomyocyte excitation-contraction coupling in an acute, in vitro setting. METHODS AND RESULTS: The functional effects of fructose on isolated adult rat cardiomyocyte contractility and Ca²⁺ handling were evaluated under physiological conditions (37°C, 2 mM Ca²⁺, HEPES buffer, 4 Hz stimulation) using video edge detection and microfluorimetry (Fura2) methods. Compared with control glucose (11 mM) superfusate, 2-deoxyglucose (2 DG, 11 mM) substitution prolonged both the contraction and relaxation phases of the twitch (by 16 and 36% respectively, p<0.05) and this effect was completely abrogated with fructose supplementation (11 mM). Similarly, fructose prevented the Ca²⁺ transient delay induced by exposure to 2 DG (time to peak Ca²⁺ transient: 2 DG: 29.0±2.1 ms vs. glucose: 23.6±1.1 ms vs. fructose +2 DG: 23.7±1.0 ms; p<0.05). The presence of the fructose transporter, GLUT5 (Slc2a5) was demonstrated in ventricular cardiomyocytes using real time RT-PCR and this was confirmed by conventional RT-PCR. CONCLUSION: This is the first demonstration of an acute influence of fructose on cardiomyocyte excitation-contraction coupling. The findings indicate cardiomyocyte capacity to transport and functionally utilize exogenously supplied fructose. This study provides the impetus for future research directed towards characterizing myocardial fructose metabolism and understanding how long term high fructose intake may contribute to modulating cardiac function

Risk factors for moderate and severe persistent pain in patients undergoing total knee and hip arthroplasty : a prospective predictive study

Persistent post-surgical pain (PPSP) is a major clinical problem with significant individual, social and health care costs. The aim of this study was to examine the joint role of demographic, clinical and psychological risk factors in the development of moderate and severe PPSP after Total Knee and Hip Arthroplasty (TKA and THA, respectively). This was a prospective study wherein a consecutive sample of 92 patients were assessed 24 hours before (T1), 48 hours after (T2) and 4-6 months (T3) after surgery. Hierarchical logistic regression analyses were performed to identify predictors of moderate and severe levels of PPSP. Four to six months after TKA and THA, 54 patients (58.7%) reported none or mild pain (Numerical Rating Scale: NRS 3). In the final multivariate hierarchical logistic regression analyses, illness representations concerning the condition leading to surgery (osteoarthritis), such as a chronic timeline perception of the disease, emerged as a significant predictor of PPSP. Additionally, post-surgical anxiety also showed a predictive role in the development of PPSP. Pre-surgical pain was the most significant clinical predictive factor and, as expected, undergoing TKA was associated with greater odds of PPSP development than THA. The findings on PPSP predictors after major joint arthroplasties can guide clinical practice in terms of considering cognitive and emotional factors, together with clinical factors, in planning acute pain management before and after surgery.This work was supported by a Project grant (PTDC/SAU-NEU/108557/2008) and by a PhD grant (SFRH/BD/36368/2007) from the Portuguese Foundation of Science and Technology, COMPETE and FEDER. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Verbal, Facial and Autonomic Responses to Empathy-Eliciting Film Clips by Disruptive Male Adolescents with High Versus Low Callous-Unemotional Traits

This study examined empathy-related responding in male adolescents with disruptive behavior disorder (DBD), high or low on callous-unemotional (CU) traits. Facial electromyographic (EMG) and heart rate (HR) responses were monitored during exposure to empathy-inducing film clips portraying sadness, anger or happiness. Self-reports were assessed afterward. In agreement with expectations, DBD adolescents with high CU traits showed significantly lower levels of empathic sadness than healthy controls across all response systems. Between DBD subgroups significant differences emerged at the level of autonomic (not verbal or facial) reactions to sadness, with high CU respondents showing less HR change from baseline than low CU respondents. The study also examined basal patterns of autonomic function. Resting HR was not different between groups, but resting respiratory sinus arrhythmia (RSA) was significantly lower in DBD adolescents with high CU traits compared to controls. Results support the notion that CU traits designate a distinct subgroup of DBD individuals

Hand osteoarthritis: clinical phenotypes, molecular mechanisms and disease management

Osteoarthritis (OA) is a highly prevalent condition and the hand is the most commonly affected site. Patients with hand OA frequently report symptoms of pain, functional limitations, and frustration in undertaking everyday activities. The condition presents clinically with changes to the bone, ligaments, cartilage and synovial tissue, which can be observed using radiography, ultrasonography or MRI. Hand OA is a heterogeneous disorder and is considered to be multifactorial in aetiology. This review provides an overview of the epidemiology, presentation and burden of hand OA, including an update on hand OA imaging (including the development of novel techniques), disease mechanisms and management. In particular, areas for which new evidence has substantially changed the way we understand, consider and treat hand OA are highlighted. For example, genetic studies, clinical trials and careful prospective imaging studies from the past 5 years are beginning to provide insights into the pathogenesis of hand OA that might uncover new therapeutic targets in disease

Environmental health guideline for Municipal Health Services : Biomonitoring for small scale chemical incidents

Er is een richtlijn ontwikkeld om te beoordelen of het zinvol is te onderzoeken of mensen als gevolg van een incident inwendig aan chemische stoffen zijn blootgesteld (biomonitoring). Het RIVM heeft de richtlijn met de GGD'en opgesteld; de GGD wordt standaard bij incidenten met chemische stoffen ingeschakeld. Na een dergelijk incident ontstaat vaak de vraag hoeveel personen daadwerkelijk aan specifieke stoffen zijn blootgesteld en in welke mate. Een meting in bloed, urine of uitgeademde lucht kan dit bevestigen. Voordelen biomonitoring: Deze metingen leveren een aantal voordelen op ten opzichte van metingen van stoffen in de lucht. Zo wordt beter inzicht verkregen in welke stoffen, en in welke mate, door het lichaam zijn opgenomen. Een ander voordeel is dat hiermee, indien relevant, het totaal aan stoffen die tijdens een incident uit verschillende bronnen zijn vrijgekomen, in het lichaam kan worden gemeten. Ook zijn inwendige blootstellingen beter in verband te brengen met eventuele gezondheidsklachten. Benodigdheden voor biomonitoring: De richtlijn maakt duidelijk bij welk type stoffen biomonitoring kan worden uitgevoerd. Afhankelijk van de stofeigenschappen zijn namelijk niet alle stoffen terug te vinden in het lichaam. Daarnaast is aangegeven welke informatie nodig is om het onderzoek technisch en logistiek uit te kunnen voeren. De richtlijn kan de GGD ook ondersteunen bij de (crisis)communicatie. Dit omvat adviezen aan het bevoegd gezag over de gezondheidsrisico's en benodigde maatregelen en onderzoek, evenals advies over de informatievoorziening naar betrokkenen. De richtlijn is vooral gericht op kleinschalige chemische incidenten.A guideline has been drawn up to assess whether people have been exposed to chemicals following a small scale incident involving chemicals. The guideline was made by the National Institute for Public Health and the Environment (RIVM) in collaboration with the Municipal Health Services (GGD). The GGD is consulted as part of standard procedure when incidents with chemicals occur. Following a chemical accident, it is important to determine the following: how many people have been affected, which substances are involved, and the extent of the exposure. This can be achieved through testing samples of blood, urine or exhaled air. Advantage of biomonitoring: The testing of clinical samples has some advantages compared with environmental measurements. For example, more information can be gained on the exact nature and the quantity of the chemicals absorbed, especially where different sources are concerned. Biomonitoring also helps to relate internal exposure to clinical symptoms. Tools necessary for biomonitoring: The guideline outlines which chemicals can be investigated with biomonitoring. This depends on the toxicokinetic properties of the chemicals. Information is also provided on the technical and logistic details necessary for testing. The guideline also acts as a support to the GGD with regard to risk-communication. This involves advising the authorities about the following: the health risks, the necessary measurements, surveillance and providing information to the general public. This guideline has been drawn up for use with small-scale chemical accidents in particular. Biomonitoring in small scale (chemical) incidents.VW