Bisphenol A exposure and cardiac electrical conduction in excised rat hearts

BACKGROUND: Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased BPA urinary concentrations and cardiovascular disease; yet the direct effects of BPA on the heart are unknown. OBJECTIVES: The goal of our studies was to measure BPA\u27s effect (0.1-100 μM) on cardiac impulse propagation ex vivo, using excised whole hearts from adult rats. METHODS: We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times. RESULTS: Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1 - 100 μM), prolonged action potential duration (1 - 100 μM) and delayed atrioventricular conduction (10 - 100 μM). Importantly, these effects were observed after acute exposure (≤ 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 μM) resulted in prolonged QRS intervals, dropped ventricular beats and eventually resulted in complete heart block. CONCLUSIONS: Our results show that acute BPA exposure slows electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA\u27s effect on heart electrophysiology and determining whether chronic in vivo exposure can cause/exacerbate conduction abnormalities in patients with pre-existing heart conditions and other high-risk populations

What we talk about when we talk about capacitance measured with the voltage-clamp step method

Capacitance is a fundamental neuronal property. One common way to measure capacitance is to deliver a small voltage-clamp step that is long enough for the clamp current to come to steady state, and then to divide the integrated transient charge by the voltage-clamp step size. In an isopotential neuron, this method is known to measure the total cell capacitance. However, in a cell that is not isopotential, this measures only a fraction of the total capacitance. This has generally been thought of as measuring the capacitance of the “well-clamped” part of the membrane, but the exact meaning of this has been unclear. Here, we show that the capacitance measured in this way is a weighted sum of the total capacitance, where the weight for a given small patch of membrane is determined by the voltage deflection at that patch, as a fraction of the voltage-clamp step size. This quantifies precisely what it means to measure the capacitance of the “well-clamped” part of the neuron. Furthermore, it reveals that the voltage-clamp step method measures a well-defined quantity, one that may be more useful than the total cell capacitance for normalizing conductances measured in voltage-clamp in nonisopotential cells

Systematic review of pre-operative exercise in colorectal cancer patients

The aim of this systematic review was to evaluate the evidence for exercise interventions prior to surgery for colorectal cancer resection. The evidence for use of exercise to improve physical fitness and surgical outcomes is as yet unknown. A systematic search was performed of MEDLINE, EMBASE, CINAHL, AMED and BNI databases for studies involving pre-operative exercise in colorectal cancer patients. Eight studies were included in the review. There is evidence that pre-operative exercise improves functional fitness, and to a lesser extent objectively measurable cardio-respiratory fitness prior to colorectal cancer resection. There is no clear evidence at present that this improvement in fitness translates into reduced peri-operative risk or improved post-operative outcomes. Current studies are limited by risk of bias. This review highlights the common difficulty in transferring promising results in a research setting, into significant improvements in the clinical arena. Future research should focus on which type of exercise is most likely to maximise patient adherence and improvements in cardio-respiratory fitness. Ultimately, adequately powered, randomised controlled trials are needed to investigate whether pre-operative exercise improves post-operative morbidity and mortality

Design of the Pacemaker REmote Follow-up Evaluation and Review (PREFER) trial to assess the clinical value of the remote pacemaker interrogation in the management of pacemaker patients

Abstract Background Although pacemakers are primarily used for the treatment of bradycardia, diagnostic data available in current pacemakers allow them to be also used as sophisticated, continuous monitoring devices. Easy access to these stored data may assist clinicians in making diagnostic and therapeutic decisions sooner, thus avoiding potential long-term sequelae due to untreated clinical disorders. Internet-based remote device interrogation systems provide clinicians with frequent and complete access to stored data in pacemakers. In addition to monitoring device function, remote monitors may be a helpful tool in assisting physicians in the management of common arrhythmia disorders. Methods The Pacemaker REmote Follow-up Evaluation and Review (PREFER) trial is a prospective, randomized, parallel, unblinded, multicenter, open label clinical trial to determine the utility of remote pacemaker interrogation in the earlier diagnosis of clinically actionable events compared to the existing practice of transtelephonic monitoring. There have been 980 patients enrolled and randomized to receive pacemaker follow up with either remote interrogation using the Medtronic CareLink® Network (CareLink) versus the conventional method of transtelephonic monitoring (TTM) in addition to periodic in-person interrogation and programming evaluations. The purpose of this manuscript is to describe the design of the PREFER trial. The results, to be presented separately, will characterize the number of clinically actionable events as a result of pacemaker follow-up using remote interrogation instead of TTM. Trial registration ClinicalTrials.gov: NCT00294645.http://deepblue.lib.umich.edu/bitstream/2027.42/112561/1/13063_2008_Article_231.pd

The association of Alu repeats with the generation of potential AU-rich elements (ARE) at 3' untranslated regions.

BACKGROUND: A significant portion (about 8% in the human genome) of mammalian mRNA sequences contains AU (Adenine and Uracil) rich elements or AREs at their 3' untranslated regions (UTR). These mRNA sequences are usually stable. However, an increasing number of observations have been made of unstable species, possibly depending on certain elements such as Alu repeats. ARE motifs are repeats of the tetramer AUUU and a monomer A at the end of the repeats ((AUUU)(n)A). The importance of AREs in biology is that they make certain mRNA unstable. Proto-oncogene, such as c-fos, c-myc, and c-jun in humans, are associated with AREs. Although it has been known that the increased number of ARE motifs caused the decrease of the half-life of mRNA containing ARE repeats, the exact mechanism is as of yet unknown. We analyzed the occurrences of AREs and Alu and propose a possible mechanism for how human mRNA could acquire and keep AREs at its 3' UTR originating from Alu repeats. RESULTS: Interspersed in the human genome, Alu repeats occupy 5% of the 3' UTR of mRNA sequences. Alu has poly-adenine (poly-A) regions at its end, which lead to poly-thymine (poly-T) regions at the end of its complementary Alu. It has been found that AREs are present at the poly-T regions. From the 3' UTR of the NCBI's reference mRNA sequence database, we found nearly 40% (38.5%) of ARE (Class I) were associated with Alu sequences (Table 1) within one mismatch allowance in ARE sequences. Other ARE classes had statistically significant associations as well. This is far from a random occurrence given their limited quantity. At each ARE class, random distribution was simulated 1,000 times, and it was shown that there is a special relationship between ARE patterns and the Alu repeats. CONCLUSION: AREs are mediating sequence elements affecting the stabilization or degradation of mRNA at the 3' untranslated regions. However, AREs' mechanism and origins are unknown. We report that Alu is a source of ARE. We found that half of the longest AREs were derived from the poly-T regions of the complementary Alu

Associations of body mass index and waist circumference with: energy intake and percentage energy from macronutrients, in a cohort of australian children

Background: It is evident from previous research that the role of dietary composition in relation to the development of childhood obesity remains inconclusive. Several studies investigating the relationship between body mass index (BMI), waist circumference (WC) and/or skin fold measurements with energy intake have suggested that the macronutrient composition of the diet (protein, carbohydrate, fat) may play an important contributing role to obesity in childhood as it does in adults. This study investigated the possible relationship between BMI and WC with energy intake and percentage energy intake from macronutrients in Australian children and adolescents