scholarly journals Ageing Related Down-Regulation of Myocardial Connexin-43 and Up-Regulation of MMP-2 May Predict Propensity to Atrial Fibrillation in Experimental Animals

2016 ◽  
pp. S91-S100 ◽  
Author(s):  
V. NAGIBIN ◽  
T. EGAN BENOVA ◽  
C. VICZENCZOVA ◽  
B. SZEIFFOVA BACOVA ◽  
I. DOVINOVA ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Matrix ◽  
Connexin 43 ◽  
Young Male ◽  
Matrix Metalloproteinase 2 ◽  
Down Regulation ◽  
Male And Female ◽  
Atrial Tissue ◽  
Age Related ◽  
Cx43 Mrna

Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties. Experiments were conducted on male and female 4-week-old and 24-week-old GPs. Atrial tissue was processed for analysis of Cx43 topology using immunohistochemistry, expression of Cx43 protein using immunobloting, and expression of mRNA of Cx43 and extracellular matrix metalloproteinase-2 (MMP-2) using real time PCR. Immunohistochemistry revealed uniform Cx43 distribution predominantly on lateral sides of the cardiomyocytes of young male and female GP atria. In contrast, non-uniform distribution, mislocalization and reduced immunolabeling of Cx43 were detected in atria of old GPs. In parallel, the atrial tissue levels of Cx43 mRNA were significantly decreased, while mRNA expression of MMP-2 was significantly increased in old versus young GPs. The changes were more pronounced in old GPs males comparing to females. Findings indicate that age-related down-regulation of atrial Cx43 and up-regulation of MMP-2 as well as disordered Cx43 distribution can facilitate development of AF in old guinea pig hearts.

scholarly journals Quantitative investigations of different vaccination policies for the control of congenital rubella syndrome (CRS) in the United Kingdom

1986 ◽  
Vol 96 (2) ◽  
pp. 305-333 ◽  
Author(s):  
R. M. Anderson ◽  
B. T. Grenfell
Keyword(s):  
Young Male ◽  
Parameter Estimates ◽  
Male And Female ◽  
Teenage Girls ◽  
Congenital Rubella ◽  
The United Kingdom ◽  
Age Related ◽  
Model Predictions ◽  
Female Children

SUMMARYThe paper examines predictions of the impact of various one-, two- and three-stage vaccination policies on the incidence of congenital rubella syndrome (CRS) in the United Kingdom with the aid of a mathematical model of the transmission dynamics of rubella virus. Parameter estimates for the model are derived from either serological data or case notifications, and special attention is given to the significance of age-related changes in the rate of exposure to rubella infection and heterogeneous mixing between age groups. Where possible, model predictions are compared with observed epidemiological trends.The principal conclusion of the analyses is that benefit is to be gained in the UK, both in the short and long term, by the introduction of a multiple-stage vaccination policy involving high levels of vaccination coverage of young male and female children (at around two years of age) and teenage girls (between the ages of 10–15 years), plus continued surveillance and vaccination of adult women in the child-bearing age classes. Model predictions suggest that to reduce the incidence of CRS in future years, below the level generated by a continuation of the current UK policy (the vaccination of teenage girls), would require high rates of vaccination > 60%) of both boys and girls at around two years of age. Numerical studies also suggest that uniform vaccination coverage levels of greater than 80–85% of young male and female children could, in the long term (40 years or more), eradicate rubella virus from the population. The robustness of these conclusions with respect to the accuracy of parameter estimates and various assumptions concerning the pattern of age-related change in exposure to infections and ‘who acquires infection from whom’ is discussed.

Longitudinal study of urinary excretion of phosphate, calcium, and uric acid in mutant NHERF-1 null mice

2006 ◽  
Vol 290 (4) ◽  
pp. F838-F843 ◽  
Author(s):  
Edward J. Weinman ◽  
Viresh Mohanlal ◽  
Nicholas Stoycheff ◽  
Fengying Wang ◽  
Deborah Steplock ◽  
...  
Keyword(s):  
Uric Acid ◽  
Urinary Excretion ◽  
Proximal Tubule ◽  
Young Male ◽  
Wild Type ◽  
Protein Targets ◽  
Male And Female ◽  
Age Related ◽  
Time Period ◽  
Apical Membranes

NHERF-1 binds numerous renal protein targets, including the proximal tubule transporters Na+/H+ exchanger 3 (NHE3) and Na+-phosphate cotransporter 2a (Npt2a). Young NHERF-1−/− male mice display defective targeting of Npt2a to apical membranes in the renal proximal tubule and manifest hypophosphatemia and increased urinary excretion of phosphate. The present studies describe the changes in the urinary excretion of phosphate, calcium, uric acid, and sodium in male and female wild-type and NHERF-1 null mice over a time period from 12 to 54 wk of age. Young male and female NHERF-1−/− mice demonstrated increased urinary excretion of phosphate and urine phosphate/creatinine ratios. There was an age-related decline in the phosphate/creatinine ratio in mutant mice such that there were no differences between wild-type and NHERF-1−/− by 24 to 30 wk of age despite the continued presence of hypophosphatemia. Male and female NHERF-1 null mice also demonstrate increased urine calcium/creatinine and uric acid/creatinine ratios compared with wild-type controls. These studies indicate defects in the renal tubule transport of phosphate, calcium, and uric acid in NHERF-1−/− male and female mice that could account for the increased deposition of calcium in the papilla of null mice.

Body Mass Index can influence Connexin 43 distribution in patients with atrial fibrillation or sinus rhythm

2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
S. Dhein ◽  
S. Rothe ◽  
A. Busch ◽  
H. Bittner ◽  
M. Kostelka ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Mass Index ◽  
Sinus Rhythm ◽  
Body Mass ◽  
Connexin 43
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