Direct effect of hypothalamic neuropeptides on the release of catecholamines by adrenal medulla in sheep - study ex vivo

Stress causes the activation of both the hypothalamic-pituitary-adrenocortical axis and sympatho-adrenal system, thus leading to the release from the adrenal medulla of catecholamines: adrenaline and, to a lesser degree, noradrenaline. It has been established that in addition to catecholamines, the adrenomedullary cells produce a variety of neuropeptides, including corticoliberine (CRH), vasopressin (AVP), oxytocin (OXY) and proopiomelanocortine (POMC) – a precursor of the adrenocorticotropic hormone (ACTH). The aim of this study was to investigate adrenal medulla activity in vitro depending, on a dose of CRH, AVP and OXY on adrenaline and noradrenaline release. Pieces of sheep adrenal medulla tissue (about 50 mg) were put on 24-well plates and were incubated in 1 mL of Eagle medium without hormone (control) or supplemented only once with CRH, AVP and OXY in three doses (10⁻⁷, 10⁻⁸ and 10⁻⁹ M) in a volume of 10 μL. The results showed that CRH stimulates adrenaline and noradrenaline release from the adrenal medulla tissue. The stimulating influence of AVP on adrenaline release was visible after the application of the two lower doses of this neuropeptide; however, AVP reduced noradrenaline release from the adrenal medulla tissue. A strong, inhibitory OXY effect on catecholamine release was observed, regardless of the dose of this hormone. Our results indicate the important role of OXY in the inhibition of adrenal gland activity and thus a better adaptation to stress on the adrenal gland level

Verapamil-L type voltage gated calcium channel inhibitor diminishes aggressive behavior in male Siamese fighting fish

Verapamil is a L-type voltage gated calcium channels inhibitor (VGCCI), which is a highly prescribed drug used in the treatment of hypertension, angina pectoris, cardiac arrhythmia and cluster headaches. Its common use caused its appearance in water environment. VGCC inhibit epinephrine release and cause many neuro-hormonal changes influencing also fish behavior. Siamese fighting fish was chosen to study the influence of verapamil given to the water on the beginning of experiment in 3 different concentrations of 0 (control), 8 and 160 μg • L-1, on aggressive behavior in these fish. The experimental fish were placed in individual glass containers for 3 weeks and the mirror test was used. The highest concentration led to a significant modulation of fish behavior after 1 week and the lower dose caused statistically significant behavioral changes after 2 weeks of verapamil treatment. Siamese fighting fish males exposed to verapamil had longer latencies to the first chase - 12.6 s (8 μg- L-1 of verapamil) and 18.8 s (160 μg • L-1 of verapamil) compared to 5.6 s in the control group, decreased attack frequency and shorter duration of these attacks. The number of attacks within 10 min was decreased from 38.3 in the control group to 27.1 and 16.1, respectively. Also the total duration of these attacks decreased from 354.8 (control) to 326.4 (decrease statistically insignificant) and to 194.8 s in verapamil treated groups. It was shown, that even relatively low concentrations of verapamil in water may have adverse effects on fish and probably other living organisms

Balance study on sheep fed with beet molasses solubles

A balance study was carried out to investigate digestibility and retention of major nutrients in wethers fed rations in which condensed beet molasses solubles (CBS)formed 27% of the dietary OM. Results showed that CBS contained 8,3 MJ of ME and 19 9 ruminal degradable protein-nitrogen and should be included in rations containing components with high ME contents. CBS with sugar beet pulp and hay in the ratio 27:57:16 on a OM basis stimulated crude fibre digestibility. The adverse effect of high levels of potassium can be offset by the inclusion of 10 9 MgO per kg CBS.'n Balansstudie is gedoen om die verteerbaarheid en retensie van die vernaamste voedingstowwe te ondersoek in hamels gevoer met rantsoene waarvan die opgeloste voedingstowwe van gekondenseerde beetmelasse (CBS)27% van die dieet OM uitgemaak het. Resultate het getoon dat CBS 8,3 MJ ME en 19 9 prote'len-stikstof wat in die grootpens afgebreek kan word, bevat en dit behoort ingesluit te word in rantsoene wat bestanddele met 'n hoe ME inhoud bevat. CBS met suikerbeetpulp en hooi in 'n verhouding van 27:57:16op 'n OM basis het ruvesel verteerbaarheid gestimuleer. Oie nadelige effek van hoe kalium vlakke kan teengewerk word deur 10 9 MgO per kg CBS in te sluit.Keywords: sheep, beet molasses solubles, digestibility, nitrogen retention, allantoin excretion, magnesium absorption, magnesium supplementation

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)