Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation

Background

Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported.

Aim

The aim was to study characteristics of induced AF and its modification by flecainide.

Methods

The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal.

Results

At AF onset, AFR was 295?±?52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269?±?36 fpm in the control group (ns), and 364?±?26 fpm in the horses with spontaneous persistent AF (P?<?0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269?±?36 fpm to a plateau of 313?±?14 fpm before decreasing to 288?±?28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P?<?0.05).

Conclusion

AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.

     

Neonatal and pubertal development in males of a cooperatively breeding primate, the cotton-top tamarin (Saguinus oedipus oedipus).

In cooperatively breeding groups of mammals, reproduction is usually restricted to a small number of individuals within the social group. Sexual development of mammals can be affected by social environment, but we know little regarding effects of the cooperative-breeding system on males. Cotton-top tamarin (Saguinus oedipus oedipus) offspring typically do not reproduce in their natal group, even though they may be physically mature. We examined neonatal and pubertal development in captive male cotton-top tamarins as an example of reproductive development within a cooperative-breeding system and to compare cotton-top tamarins with the general primate model. Puberty was characterized using both hormonal and physical measures. Data were collected on urinary levels of LH, testosterone (T), dihydrotestosterone (DHT), cortisol, and the ratio of DHT to T; testicular development; body weight; and breeding age. We determined that 1) pubertal LH secretion began at Week 37, 2) a surge of T secretion followed at Weeks 41-44, and 3) an increase in the metabolism of T to DHT may have occurred at an average age of 48.6 wk. Most of the rapid weight gain was completed by Week 24, before hormonal increases and rapid scrotal growth. We concluded that rapid pubertal testicular growth in captive cotton-top males was completed by an average 76 wk, but that completion of the individual pubertal spurt can occur between 56 and 122 wk. In a cooperative-breeding system, the opportunity for successful reproduction is dictated by the social environment, but we found no evidence that male offspring were developmentally suppressed in their natal social groups. Our findings suggest that puberty in male New World callitrichid primates occurs more quickly than puberty in Old World primates, even though both have similar patterns of development.     

Three-dimensional structure of phosphorylase kinase at 22 A resolution and its complex with glycogen phosphorylase b.

Phosphorylase kinase (PhK) integrates hormonal and neuronal signals and is a key enzyme in the control of glycogen metabolism. PhK is one of the largest of the protein kinases and is composed of four types of subunit, with stoichiometry (alphabetagammadelta)(4) and a total MW of 1.3 x 10(6). PhK catalyzes the phosphorylation of inactive glycogen phosphorylase b (GPb), resulting in the formation of active glycogen phosphorylase a (GPa) and the stimulation of glycogenolysis. We have determined the three-dimensional structure of PhK at 22 A resolution by electron microscopy with the random conical tilt method. We have also determined the structure of PhK decorated with GPb at 28 A resolution. GPb is bound toward the ends of each of the lobes with an apparent stoichiometry of four GPb dimers per (alphabetagammadelta)(4) PhK. The PhK/GPb model provides an explanation for the formation of hybrid GPab intermediates in the PhK-catalyzed phosphorylation of GPb.     

Crystallography and luminescence of divalent osmium complexes green osmium emitters and possible evidence for d-orbital backbonding

The preparation, photophysics, and solid-state structures of three osmium cored complexes are reported. The osmium complexes take the general form of [OsCl(N-N)(L-L)(CO)]⁺ hexafluorophosphate where N stands for a derivative of 1,10-phenanthroline and L stands for a phosphine type ligand. The emission of the complexes is shown to be blue shifted to the osmium emission of Os(bpy)₃ ²⁺. The emissions of the various complexes range from yellow (560 nm) to yellow-green (550 nm) to green (520 nm). The quantum yields vary between 60% and 75%. The complexes show lifetimes that are much longer than expected with ranges of 6.5-38 μs. Crystallographic results show that the carbonyl is trans to a phenanthroline nitrogen and the chloro ligand is trans to phosphorus. A discussion will be presented as to the nature of the bonding in these complexes based upon the data from the crystallography.     

Movement of Viruses between Biomes

Viruses are abundant in all known ecosystems. In the present study, we tested the possibility that viruses from one biome can successfully propagate in another. Viral concentrates were prepared from different near-shore marine sites, lake water, marine sediments, and soil. The concentrates were added to microcosms containing dissolved organic matter as a food source (after filtration to allow 100-kDa particles to pass through) and a 3% (vol/vol) microbial inoculum from a marine water sample (after filtration through a 0.45-μm-pore-size filter). Virus-like particle abundances were then monitored using direct counting. Viral populations from lake water, marine sediments, and soil were able to replicate when they were incubated with the marine microbes, showing that viruses can move between different ecosystems and propagate. These results imply that viruses can laterally transfer DNA between microbes in different biomes.     

Immunotoxicity Biomarkers in Fish: Development,Validation and Application for Field Studies and Risk Assessment

Imunocompetence is usually monitored using a tiered approach that is based upon several parameters including immunopathology, immune function, and host resistance. Through the efforts of numerous investigations, well-characterized immune assays validated in rodents for their sensitivity and reproducibility in assessing xenobiotic-induced immunotoxicity are currently available. Recently, many of these same endpoints have been utilized in non-mammalian species as indicators to predict chemical-induced immunotoxicity. In this laboratory, immune assays that measure immunopathology, antibody-forming cell response to T-dependent antigens, lymphocyte proliferation, macrophage function, antioxidant activity, and host resistance against infectious bacteria have been employed successfully to assess metal-, pesticide-, aromatic hydrocarbon-, and mixture-induced immunotoxicity in laboratory-reared Japanese medaka (Oryzias latipes). These same assays have also proven successful in feral fish populations for predicting risk(s) associated with habitation in contaminated aquatic environments. For example, smallmouth bass (Micropterus dolomieu) collected from a polychlorinated biphenyl-contaminated site had reduced phagocyte function, oxyradical production, and antioxidant levels (compared to reference fish), while circulating leukocyte profiles and lymphocyte proliferation by splenic T-cells were altered in organochlorine-exposed walleye (Stizostedium vitreum vitreum). Results of the aforementioned studies demonstrate that immune assays developed and validated in a laboratory fish model can be successfully applied to feral fish populations to predict the toxicological hazards associated with exposure to immunomodulating aquatic pollutants.     

Japanese quail microsatellite loci amplified with chicken-specific primers

Forty-eight primer pairs for chicken (Gallus gallus) microsatellite loci were tested in polymerase chain reaction (PCR) amplification of Japanese quail (Coturnix japonica) genomic DNA. Amplification products were obtained from 28 primer-pairs (58.3%) after optimizing the PCR conditions. Eleven (22.9%) of these generated specific products and 17 yielded non-specific amplification products. Eight markers (ADL0037, ADL0038, ADL0142, ADL0143, ADL0206, ADL0315, ADL0366, and HUJ0006) were polymorphic and three were monomorphic (ADL0023, ADL0024, and ADL0257) in four Japanese quail populations. Specific amplification products from each of the 11 PCR primers were sequenced. Seven of the eight polymorphic and one of three monomorphic markers contained simple tandem repeats. Six of these microsatellite loci (ADL0037, ADL0315, ADL0142, ADL0143, ADL0366 and ADL0257) may be homologous to the corresponding chicken loci from which the markers were developed.