Canine ACP prepared according to the manufacturer's recommendations, or by using a softer spin does not show the same specifications as human ACP, which shows a doubling in platelet count compared to WB. Even though canine ACP has a similar number of platelets per injected volume and consequently, probably the same amount of injected growth factors than WB, application of canine ACP would not be associated with the proinflammatory potential reported for WB, as it is almost free of erythrocytes and nucleated cells.
To clarify whether ototopical glucocorticoid treatment is associated with impaired hypothalamic-pituitary-adrenal axis (HPA) activity and altered hepatic metabolism, one commercially available dexamethasone-containing ointment was tested. At present, very little is known about the effects of ototopical glucocorticoid treatment on HPA and liver function. Ten beagle dogs received two daily therapeutic doses of dexamethasone (0.6 mg/ear) in the outer auditory canal for 21 d in a single-blind, placebo-controlled study. Resting cortisol concentrations were assessed before, during, and after treatment using an RIA system. Adrenal function and HPA feedback sensitivity were measured by a standard dose (250 microg) ACTH stimulation test. Serum biochemical and hematological parameters were measured, whether ototopical glucocorticoids affect hepatic function was studied, and blood cell counts were made. Ototopical dexamethasone treatment induced a marked suppression (to about 100%) of resting plasma cortisol concentrations below the placebo effect (P < 0.0001) within the first 11 d, and these remained reduced during the entire treatment period up to d 19. As well, an ACTH stimulation test found a markedly reduced rise in plasma cortisol concentrations (P = 0.0004). Concomitantly, significant increases in serum activities of alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase were detected. Moreover, we found a significant reduction in differential leukocyte counts of eosinophils and lymphocytes, whereas neutrophils increased. Although cortisol levels and hematological parameters returned to baseline 7 d after treatment cessation, liver enzyme activities remained elevated. In conclusion, these findings suggest that after ototopical application, dexamethasone is sufficiently absorbed from the auditory canal to suppress HPA function as well as to alter metabolic and hemopoietic profiles. Thus, in long-term treatment of otitis externa or media, the systemic adverse suppression of HPA has to be considered in relation to stress exposure, whereas changes in serum enzyme activities may not be interpreted as hepathopathy.
ZusammenfassungThrombozytenkonzentrate (TZK) werden gegenwärtig in der Pferdeorthopädie häufig therapeutisch eingesetzt. Bei dieser autologen Therapieform werden Thrombozyten (TZ) in das geschädigte Gewebe appliziert, damit sie ihre heilungsfördernden Wachstumsfaktoren (GF) lokal freisetzen können. Zu den wichtigsten GF für die Gewebsregeneration zählen PDGF-BB (platelet-derived growth factor BB) und TGF-b 1 (transforming growth factor b 1 ). Autologous Conditioned Plasma ® (ACP) stellt eine relativ neue, einfache und schnell aufzubereitende Form eines TZK aus der Humanmedizin dar. In dieser Studie kommt ein patentiertes Doppelspritzensystem (ACP ® -Spritzen) zum Einsatz, dessen optimale Zentrifugationsparameter (Laufzeit und Umdrehungen/Min (U/min)) für die ACP-Herstellung aus Pferdeblut etabliert werden sollen. Diese Parameter wurden anhand der Blutzellen-und GF-Konzentrationen im ACP im Vergleich zu den Basiswerten im Vollblut bestimmt. Im ersten Teil der Studie wurde von zehn gesunden Warmblutpferden ein großes Blutbild angefertigt, um die Basiswerte der Blutzellkonzentration zu erhalten. Die Blutentnahme für die ACP-Proben erfolgte in den ACP ® -Spritzen. Pro Pferd wurden zwölf Proben entnommen. Die Aufbereitung jeder Probe erfolgte in zwölf verschiedenen Varianten, wobei jeweils unterschiedliche Zentrifugationsparameter gewählt wurden (U/min; Laufzeit). Folgende Parameter wurden getestet: 900 (≙127 xg), 1100 (≙189 xg), 1300 (≙265 xg) und 1500 (≙352 xg) U/min mit einer Laufzeit von 4, 5 bzw. 6 Minuten. In jeder ACP-Probe wurden die Blutzellkonzentrationen gemessen und mit den Basiswerten, die vorab im Vollblut bestimmt wurden, verglichen. Daraus resultierte die Bestimmung der Konzentrationen von PDGF-BB und TGF-b 1 nach drei verschiedenen Zentrifugationsregimen (900 U/min x 4 min, 1100 U/min x 5 min und 1300 U/min x 6 min) und deren vergleichende Betrachtung. Im zweiten Teil der Studie wurde konventionelles Plasma von zehn anderen gesunden Warmblutpferden hergestellt und die Blutzellenkonzentrationen sowie die GF-Konzentrationen (TGF-b 1 und PDGF-BB) mit denen aus einer ausgewählten ACP-Probe (1100 U/min x 5 min) für jedes Pferd verglichen, um die Ergebnisse dieser Studie zu validieren. Mit höherer Umdrehungszahl und län-gerer Laufzeit konnte ein tendenzieller Abfall der Thrombozyten-(TZ) und Leukozyten-(LZ) Konzentration beobachtet werden, Erythrozyten (EZ) wurden bei jeder Kombination aus dem Plasma eliminiert. Bei der Kombination 1100 U/min x 5 min lag die Erhöhung der TZ-Konzentration bei 149 % (±20) oder 219 G/L (±61). Die LZ wurden dabei auf 12% minimiert (0,79 x 10 9 Zellen/L). Die Konzentration von PDGF-BB und TGF-b 1 lagen bei 1,58 ng/ml bzw. 1,40 ng/ml. Zwischen den drei ausgewählten Kombinationen zeigten sich keine signifikanten Unterschiede im Hinblick auf die GF-Konzentration. Im Hinblick auf die TZ-, LZ-, GF-Konzentration ergab die Kombination aus 1100 U/min x 5 min im Gesamtbild die besten Ergebnisse.Die TZ-und GF-Werte im ACP waren signifikant höher verglichen mit jenen im konventionellen Pl...
Gestational diabetes and impaired glucose tolerance in pregnancy were found to be important teratogenetic risk factors for the development of diabetes in the offspring. Mechanisms of action and prevention of maternofetal transmission of teratogenetic susceptibility to diabetes are presented. Gestational diabetes induced in the F0 generation produced the following effects in the F1 and/or F2 generation: Early postnatal hyperinsulinaemia, decreased noradrenaline and serotonin and increased endorphin concentrations in specific brain regions, permanent hypoplasia of the hypothalamic ventromedial nuclei, decreased insulin responsiveness to glucose, impaired glucose tolerance and increased diabetes susceptibility.
In order to maximize their fitness, organisms in seasonal environments rely on external cues to optimally time their life‐history stages. One of the most important zeitgeber to time reproduction is the photoperiod, but further environmental cues are assessed to fine‐tune reproduction due to year‐to‐year variation in environmental conditions. However, in urbanized environments, the pervasive artificial light at night has altered the natural signal of light and darkness. Accordingly, artificial light at night was repeatedly shown to affect avian reproductive physiology and to advance seasonal reproduction in birds. However, these experiments were mainly conducted in the absence of further environmental cues to facilitate the investigation of the mechanisms which are still poorly understood. Here, we investigate whether the endocrine system of free‐ranging European blackbirds (Turdus merula) correlates with the amount of artificial light at night along a rural to urban gradient while the birds still encounter complementary environmental cues including seasonal variation in day length and temperature. Testosterone and estrone were assessed as metabolites in fecal samples and corticosterone in blood from mist‐netted blackbirds. We demonstrate that seasonal fluctuations in abiotic factors, individual conditions, but also light at night affect the reproductive and stress physiology of wild European blackbirds. Elevated artificial night light intensities were significantly positively correlated with corticosterone and negatively with female estrone levels. No effects of artificial light were found for testosterone levels. Our results suggest that female blackbirds in particular perceive even low levels of artificial light at night as a weak but chronic stressor that interacts with the hypothalamic‐pituitary‐gonadal axis and leads to a reduced secretion of reproductive hormones. These findings point out that the impacts of light pollution are diverse and we only slowly disentangle its multiple effects on physiology, ecology, and biodiversity.
β2-Agonists blunt the function of the β-adrenoceptor G-protein adenylate cyclase-signalling system, whereas glucocorticoids reverse the agonist-mediated diminished β-adrenergic responses; however, these effects have not been reported in vivo in calf lymphocytes. In this study, we first investigated the presence of the β2-adrenergic receptors on calf lymphocytes, and second we tested the effects of either clenbuterol alone or in combination with dexamethasone on receptor expression and function (isoproterenol-induced intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) formation) in vivo. (–)-[125I]-Iodocyanopindolol (ICYP) binding to intact calf lymphocytes was rapid, saturable (maximal number of binding sites 987 ± 89 ICYP-binding sites/cell, n = 4) and of high affinity (KD value 17.23 ± 2.8 pmol/l, n = 4). These binding sites were of the β2-subtypes of adrenoceptors as indicated by the fact that β-agonists inhibited ICYP binding with an order of potency: (–)-isoproterenol > (–)-adrenaline > (–)-noradrenaline. Furthermore, the selective β2-adrenoceptor antagonist ICI 118.551 was about >1,500 times more potent in inhibiting ICYP binding than was the β1-selective adrenoceptor antagonist CGP 20712A. Consequently, calves were treated with clenbuterol (1.0 µg/kg b.i.d., i.v.) for 9 days alone or simultaneously with dexamethasone (0.1 mg/kg, i.v., once a day for 4 days). Clenbuterol decreased the number of lymphocyte β2-adrenergic receptors by about 40–50% after only 48 h of drug administration. This was accompanied by a decrement in isoproterenol-induced lymphocyte cAMP formation. Upon application of both drugs, dexamethasone restored the clenbuterol-mediated decrease in β2-adrenoceptors and cAMP production. Dexamethasone elevated the number of β2-adrenoceptors and cAMP almost 1.5- to 2-fold at 24 h of drug administration, an effect that persisted for up to 24 h following drug withdrawal. Neither clenbuterol nor the combination with dexamethasone had an influence on the affinity of the receptor for the ligand. The present results demonstrate that dexamethasone in vivo upregulates the number and function of calf lymphocyte β2-adrenoceptors, and thus enhances the sensitivity of the β2-adrenoceptor signal-transduction pathway for clenbuterol during concomitant treatment with both drugs.
In the transition period from late gestation to early lactation, dairy cows undergo tremendous metabolic changes. Insulin is a relevant antilipolytic factor. Decreasing serum concentrations of insulin and glucose, increasing serum concentrations of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHB), and changes in body condition score (BCS) reflect the negative energy balance around calving. This study investigated peripartum metabolic adaptation in 359 primiparous and 235 multiparous German Holstein cows from a commercial dairy herd under field conditions. Body condition score was recorded and blood samples were taken 10 to 1 d prepartum, 2 to 4 d postpartum, and 12 to 20 d postpartum. Generalized mixed models and generalized estimation equations were applied to assess associations between prepartum BCS; BCS changes during the transition period; insulin, glucose, NEFA, and BHB serum concentrations; and milk yield, which was taken from an electronic milk meter from d 6 of lactation. Serum insulin concentrations of multiparous postpartum cows were lower compared with prepartum, and compared with primiparous cows. In general, primiparous cows had lower postpartum NEFA and BHB concentrations than multiparous cows. In primiparous cows, we identified a positive association between prepartum BCS and prepartum serum insulin concentration. Prepartum obese multiparous cows, but not primiparous cows, were characterized by higher postpartum serum NEFA and BHB concentrations and lower milk yield than other cows in the same parity class. Primiparous cows with a smaller degree of BCS loss during the transition period had higher postpartum insulin and lower NEFA concentrations and lower milk yield than other primiparous cows. In conclusion, primiparous cows had less lipolysis and lower milk yield than multiparous cows, associated with higher insulin concentrations. Avoiding high body condition loss during the transition period is a main factor in preventing peripartal metabolic imbalances of glucose and fat metabolism.
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