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

Psychosocial Factors Associated with Patterns of Smoking Surrounding Pregnancy in Fragile Families

Although research has documented factors associated with maternal smoking, we need a more in-depth understanding of the risk factors associated with changes in smoking behaviors during the postpartum period. We investigate smoking patterns during pregnancy and 1 year postpartum as a function of relevant psychosocial factors. We use data on 3,522 postpartum mothers from the Fragile Families and Child Wellbeing Study to analyze the predictors of smoking among mothers who did not smoke during pregnancy but smoked at 1 year postpartum, mothers who smoked both during pregnancy and postpartum, and mothers who did not smoke during either period. Our covariates are grouped into four categories of risk factors for smoking: socioeconomic status, health care, life course and health, and partner and social support. Postpartum mothers in our sample were more likely to smoke throughout or after their pregnancies if they had only a high school education or less, had a household income three or more times below the poverty line, had public or no health insurance, breastfed for less than 5 months, were not married to the infant’s father, if the infant’s father currently smoked, and if they attended religious services less than once a week. Mental health problems were consistently associated with an increased risk of constant and postpartum smoking relative to non-smoking. Psychosocial factors play a role in postpartum smoking, but they have a stronger effect in predicting smoking that persists throughout pregnancy and the first year postpartum

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

Evaluation of the Role of Candida albicans Agglutinin-Like Sequence (Als) Proteins in Human Oral Epithelial Cell Interactions

The fungus C. albicans uses adhesins to interact with human epithelial surfaces in the processes of colonization and pathogenesis. The C. albicans ALS (agglutinin-like sequence) gene family encodes eight large cell-surface glycoproteins (Als1-Als7 and Als9) that have adhesive function. This study utilized C. albicans Δals mutant strains to investigate the role of the Als family in oral epithelial cell adhesion and damage, cytokine induction and activation of a MAPK-based (MKP1/c-Fos) signaling pathway that discriminates between yeast and hyphae. Of the eight Δals mutants tested, only the Δals3 strain showed significant reductions in oral epithelial cell adhesion and damage, and cytokine production. High fungal:epithelial cell multiplicities of infection were able to rescue the cell damage and cytokine production phenotypes, demonstrating the importance of fungal burden in mucosal infections. Despite its adhesion, damage and cytokine induction phenotypes, the Δals3 strain induced MKP1 phosphorylation and c-Fos production to a similar extent as control cells. Our data demonstrate that Als3 is involved directly in epithelial adhesion but indirectly in cell damage and cytokine induction, and is not the factor targeted by oral epithelial cells to discriminate between the yeast and hyphal form of C. albicans

Phage Displayed Short Peptides against Cells of Candida albicans Demonstrate Presence of Species, Morphology and Region Specific Carbohydrate Epitopes

Candida albicans is a commensal opportunistic pathogen, which can cause superficial infections as well as systemic infections in immuocompromised hosts. Among nosocomial fungal infections, infections by C. albicans are associated with highest mortality rates even though incidence of infections by other related species is on the rise world over. Since C. albicans and other Candida species differ in their susceptibility to antifungal drug treatment, it is crucial to accurately identify the species for effective drug treatment. Most diagnostic tests that differentiate between C. albicans and other Candida species are time consuming, as they necessarily involve laboratory culturing. Others, which employ highly sensitive PCR based technologies often, yield false positives which is equally dangerous since that leads to unnecessary antifungal treatment. This is the first report of phage display technology based identification of short peptide sequences that can distinguish C. albicans from other closely related species. The peptides also show high degree of specificity towards its different morphological forms. Using fluorescence microscopy, we show that the peptides bind on the surface of these cells and obtained clones that could even specifically bind to only specific regions of cells indicating restricted distribution of the epitopes. What was peculiar and interesting was that the epitopes were carbohydrate in nature. This gives insight into the complexity of the carbohydrate composition of fungal cell walls. In an ELISA format these peptides allow specific detection of relatively small numbers of C. albicans cells. Hence, if used in combination, such a test could help accurate diagnosis and allow physicians to initiate appropriate drug therapy on time

Prognostic implications of negative dobutamine stress echocardiography in African Americans compared to Caucasians

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Mathematical model describing erythrocyte sedimentation rate. Implications for blood viscosity changes in traumatic shock and crush syndrome

BACKGROUND: The erythrocyte sedimentation rate (ESR) is a simple and inexpensive laboratory test, which is widespread in clinical practice, for assessing the inflammatory or acute response. This work addresses the theoretical and experimental investigation of sedimentation a single and multiple particles in homogeneous and heterogeneous (multiphase) medium, as it relates to their internal structure (aggregation of solid or deformed particles). METHODS: The equation system has been solved numerically. To choose finite analogs of derivatives we used the schemes of directional differences. RESULTS: (1) Our model takes into account the influence of the vessel wall on group aggregation of particles in tubes as well as the effects of rotation of particles, the constraint coefficient, and viscosity of a mixture as a function of the volume fraction. (2) This model can describe ESR as a function of the velocity of adhesion of erythrocytes; (3) Determination of the ESR is best conducted at certain time intervals, i.e. in a series of periods not exceeding 5 minutes each; (4) Differential diagnosis of various diseases by means of ESR should be performed using the aforementioned timed measurement of ESR; (5) An increase in blood viscosity during trauma results from an increase in rouleaux formation and the time-course method of ESR will be useful in patients with trauma, in particular, with traumatic shock and crush syndrome. CONCLUSION: The mathematical model created in this study used the most fundamental differential equations that have ever been derived to estimate ESR. It may further our understanding of its complex mechanism

Heterogeneous patterns of tissue injury in NARP syndrome

Point mutations at m.8993T>C and m.8993T>G of the mtDNA ATPase 6 gene cause the neurogenic weakness, ataxia and retinitis pigmentosa (NARP) syndrome, a mitochondrial disorder characterized by retinal, central and peripheral neurodegeneration. We performed detailed neurological, neuropsychological and ophthalmological phenotyping of a mother and four daughters with NARP syndrome from the mtDNA m.8993T>C ATPase 6 mutation, including 3-T brain MRI, spectral domain optical coherence tomography (SD-OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), electromyography and nerve conduction studies (EMG-NCS) and formal neuropsychological testing. The degree of mutant heteroplasmy for the m.8993T>C mutation was evaluated by real-time allele refractory mutation system quantitative PCR of mtDNA from hair bulbs (ectoderm) and blood leukocytes (mesoderm). There were marked phenotypic differences between family members, even between individuals with the greatest degrees of ectodermal and mesodermal heteroplasmy. 3-T MRI revealed cerebellar atrophy and cystic and cavitary T2 hyperintensities in the basal ganglia. SD-OCT demonstrated similarly heterogeneous areas of neuronal and axonal loss in inner and outer retinal layers. AOSLO showed increased cone spacing due to photoreceptor loss. EMG-NCS revealed varying degrees of length-dependent sensorimotor axonal polyneuropathy. On formal neuropsychological testing, there were varying deficits in processing speed, visual–spatial functioning and verbal fluency and high rates of severe depression. Many of these cognitive deficits likely localize to cerebellar and/or basal ganglia dysfunction. High-resolution retinal and brain imaging in NARP syndrome revealed analogous patterns of tissue injury characterized by heterogeneous areas of neuronal loss