Bovine dopamine type-2 receptor SNP has no effect on growth, semen characteristics and prolactin concentrations in beef bulls treated with a dopamine agonist.

A dopamine type-2 receptor (DRD2) SNP, previously found to be correlated with serum prolactin (PRL) concentrations in cattle, was evaluated for impact on growth traits, serum prolactin concentration, and semen quality. Over a four-year period, yearling beef bulls were allowed diets containing or lacking ergot alkaloids (EA). Every 21 or 28 d semen was collected for semen motility and morphology assessment and blood samples were collected to measure serum PRL concentrations. In addition, body condition score and scrotal circumference were evaluated. Serum PRL concentrations were assessed using a radioimmunoassay. In the first year, all bulls were sacrificed at the end of a 126-day study. Testicles and epididymis were collected at the end of the study or 60 days after removal from treatment. Immunohistochemistry was performed on testis, epididymis, and sperm cells, incubated with or without a primary antibody for DRD2 and counterstained with DAPI. Isolation of DNA was performed on sperm pellets using DNAzol (Thermo Fisher Scientific, Waltham, MA, USA) methods. Polymerase chain reaction was performed to amplify the region of the DRD2 gene containing the SNP of interest. The products were subjected to restriction fragment length polymorphism analysis. Further, all samples were subjected to genotyping using a custom Taqman genotyping assay (Applied Biosystems, Foster city, CA, USA). The presence of DRD2 was detected in the testis, epididymis, and sperm cells. The DRD2 genotype was not associated with semen quality, serum PRL, or growth traits. Consumption of EA resulted in lesser PRL serum concentrations but had no effect on values for other variable examined.

Assessment of semen quality and fertility in young growing beef bulls exposed to ergot alkaloids.

The objective of this study was to evaluate semen quality and fertility in beef bulls grazing the ergot alkaloid (EA) producing tall fescue cultivar, Kentucky 31 (KY31), compared to a novel endophyte (NE) cultivar lacking EA. Two studies were conducted over a 3-year period. In studies 1 (n = 10; ages ≥ 24 mo) and 2 (n = 53 over two years; ages 12-16 mo), Angus (AN) bulls were stratified by body weight (BW), body condition score (BCS), and scrotal circumference (SC), and then allotted to graze either KY31 or NE for 56 days. Semen samples were collected, and BW, BCS, and SC were evaluated at the start of treatment (TRT) on day (d) 0 and every 28 days to the end of each study. In addition, blood samples were collected on d 0 and every 28 days for assessment of circulating prolactin (PRL) levels in study 2. On d 56, for both studies, semen from bulls (n = 2 per treatment in study 1 and n = 4 per treatment in study 2) with similar and acceptable quality were extended, kept at 19° C, and used for timed artificial insemination (TAI) of primi- and multiparous AN and AN- crossbred females. Pregnancy was evaluated at 35 and 90 days post-TAI via transrectal ultrasonography to determine pregnancy rates. Serum PRL concentrations showed a TRT by d effect (P ≤ 0.05), with values for bulls grazing KY31 decreased on d 28 and d 56 of grazing compared to NE. In studies 1 and 2, bull BW and BCS were affected by d (P ≤ 0.05), but not by TRT. No TRT or TRT by d effect on semen quality was observed in either study; however, d impacted both velocity and concentration in study 2 (P ≤ 0.05). In study 1, TAI pregnancy rates at 35 days post-TAI were lower (P ≤ 0.05) in the group inseminated with semen from bulls grazing KY31; however, in study 2, pregnancy rates did not differ due to treatment 35 post-TAI (P > 0.05). Grazing KY31 negatively impacted serum PRL concentrations, supporting previous observations; however, consumption of KY31 had no effect on growth or semen quality of AN bulls ranging from 12 to ≥24 mo of age. Furthermore, fertility data is inconsistent between studies and requires further investigation.

Effects of grazing tall fescue containing ergot alkaloids on bull sperm cryopreservation.

There are many positive agronomic traits that make tall fescue a desirable forage, however, reduced fertility rates are reported for beef cattle grazing pasture containing the ergot alkaloid-producing endophyte, Epichloë coenophiala. The objective of this study was to assess the influence of consuming tall fescue containing ergot alkaloids on sperm physiology, as measured by survival of sperm following cryopreservation. Yearling Angus bulls (n=25), having passed a breeding soundness exam (BSE), were assigned to one of two treatments accounting for body weight (BW) and body condition score (BCS). Bulls were allotted to one of two treatments on day (d) 0, grazing toxic Kentucky 31 (KY31) or a novel endophyte-containing cultivar, Texoma Max Q II (NE; AR584 Ag Research) that does not produce ergot alkaloids, for 112 days. On d 112, all bulls were placed on NE pasture to the end of test (d 168) to evaluate recovery from grazing KY31. Blood, urine, and semen samples were collected every 28 days. Semen collected on d 28, 84, 112, 140, and 168 was extended, frozen, thawed 48h later, and subjected to analyses. There were significant treatment by day interactions for serum prolactin (PRL) concentrations, verifying the effectiveness of treatment (P<0.05). Serum PRL concentrations were less in the bulls pastured on KY31 compared to NE on d 28, 84, and 112. Urinary alkaloid concentrations were affected by treatment by day interactions, confirming ergot alkaloids were present in animal systems (P<0.05). Bulls in the NE treatment group had lesser urinary alkaloid concentrations than those pastured on KY31 on d 28, 84, and 112. Post-thaw sperm analyses revealed that the percentage of progressively motile sperm was less in bulls pastured on KY31 when compared to NE (P<0.05). There were treatment by day interactions for sperm concentration, percent motile sperm, percent motile sperm concentration, and percent progressively motile sperm concentration post-thawing (P<0.05). The KY31 treatment group had a lesser sperm 1) concentration than the NE group on d 84; 2) percent motility on d 28, 84, and 168; 3) motile concentration on d 28, 84, and 168; and 4) progressively motile concentration on d 28 and 84. Sperm motility was affected post-thawing for at least 56 d following removal from the KY31 pasture.

Treatment of multifocal atrial tachycardia with metoprolol.

We used metoprolol orally or iv in 25 patients with multifocal atrial tachycardia that was complicating severe cardiopulmonary illness, and we observed its effect on heart rate and rhythm, BP, and arterial blood gases. All patients showed a dramatic slowing of heart rate, averaging 54.0 +/- 4.0 beat/min (p less than .001), with only small and transient fall in BP. Seventeen (68%) patients experienced conversion to sinus rhythm, 11 immediately, and six more within 3 h. Time to response averaged 5.1 h with the oral form but was less than 10 min when the drug was given iv. The mean oral dose required was 32.5 mg, and the mean iv dose was 6.5 mg. No patient experienced clinically apparent hemodynamic or respiratory deterioration as a result of metoprolol administration. While arterial pH and PaCO2 were unaltered by metoprolol, mean PaO2 increased by 12.2 +/- 5.8 torr (p less than .05), the increase being greatest in patients with more severe gas-exchange derangement. We conclude that metoprolol is effective in the management of multifocal atrial tachycardia.

Verapamil in multifocal atrial tachycardia. Hemodynamic and respiratory changes.

The hemodynamic and gas exchange alterations resulting from treatment of multifocal atrial tachycardia (MAT) with intravenous verapamil were monitored in 13 critically ill patients. Administration of verapamil (mean dose 12.9 +/- 1.0 mg) produced immediate if usually transient reduction in heart rate. Stroke volume index rose, but no significant changes in cardiac index, blood pressure, or pulmonary artery or capillary wedge pressures were demonstrated. Verapamil appeared to increase pulmonary venous admixture. Oxygen transport, however, did not decrease significantly. Verapamil is generally beneficial in the treatment of MAT, but its utility may be limited in many patients by its tendency to aggravate pre-existing arterial hypoxemia.

Glucocorticoid effects on the embryonic chick heart. I. Glucocorticoid enlargement of the heart.

Cortisol increases the heart weight relative to body weight following injection of growth suppressing amounts of the hormone on incubation days 9, 10, 13, and 15. Hormone administration increases glycogen, glycosaminoglycan (GAG), and total lipid concentration in the embryonic myocardium. Deoxyribonucleic acid (DNA) and protein concentration are decreased proportionally. Glycogen synthetase and radiosulphate incorporation into GAG are increased by the glucocorticoid. Lack of growth inhibition of the embryonic myocardium by glucocorticoids is not due to absence of glucocorticoid receptors. [3H]-Dexamethasone was shown to bind to a cytoplasmic and nuclear fraction of the chick heart. Binding to a cytoplasmic protein could be demonstrated in the heart at nine days of embryonic development and increased with developmental age. The increase in cardiac mass appears to be specific for the glucocorticoid hormones when compared with epinephrine and deoxycorticosterone. The latter two hormones did not increase cardiac mass.

Alterations in cartilage metabolism by neurostimulant drugs.

Suppression of growth without significant alterations in hormonal patterns has been demonstrated for the neurostimulant drug pemoline. Comparison of the in vitro effect of pemoline, methylphenidate, and methamphetamine on somatomedin-stimulated sulfate uptake by cartilage showed all three drugs to be inhibitory. Sulfate uptake by cartilage can be directly related to growth and glycosaminoglycan biosynthesis. Assay of two of the enzymes involved in the glycosaminoglycan biosynthetic pathway showed that methamphetamine and methylphenidate caused a marked depression of xylosyl- and galactosyltransferase enzyme activity. These data suggest an interference with cartilage metabolism as one possible mechanism for the growth retardation observed in children on neurostimulant drug therapy.