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The aim of the present study was to evaluate the stimulating effect of synthetic GnRH analogues without the use of prostaglandins on ovarian follicular growth dynamic and oestrus. The study was made on 30, 3 to 9-year-old Lithuanian Black and White (LBW) and German Black and White (GBW) breed cows. The study was conducted in the Lithuanian Veterinary Academy practical training and research farm. Oestrus in 23 cows was stimulated using synthetic GnRH analogues Dalmarelin (Lecirelin) (Fatro S. p. A., Italy) and in 14 cows with the use of Depherelin® (Gonavet® 50, Veyx-Pharma GmbH, Germany). Dalmarelin (Lecirelin) induced oestrus in 100% of the stimulated cows, and Depherelin® (Gonavet® 50) induced oestrus in 92.9 % of stimulated cows. Following an injection of synthetic GnRH analogues, preparations Depherelin® and Dalmarelin, plasma progesterone concentration decreased, due to the ovulation of dominant follicle or onset of the new follicular wave. Cows stimulated with Dalmarelin had a faster follicular growth rate and bigger size of follicles at ovulation compared to Depherelin® and control group cows (p = 0.05). In the pregnancy trial that followed 45 days after artificial insemination, the highest percentage (43.5 %) of pregnant cows was determined in the group of cows stimulated with Dalmarelin.
Synthetic analogs of vitamin D for potential use in differentiation therapy should se­lectively regulate genes necessary for differentiation without inducing any perturba­tions in calcium homeostasis. PRI-1906, an analog of vitamin D2, and PRI-2191, an analog of vitamin D3 bind nuclear vitamin D receptor (nVDR) with substantially lower affinity than 1,25-dihydroxyvitamin D3 (1,25-D3), but have higher differentiation-in­ducing activity as estimated in HL-60 leukemia cell model. To examine how their in­creased differentiation-inducing activity is regulated we tested the hypothesis that membrane-mediated events, unrelated to nVDR, take part in the differentiation in re­sponse to PRI-1906 and PRI-2191. The induction of leukemia cell differentiation in response to the analogs of vitamin D was inhibited by LY294002 (phosphatidyl- inositol 3-kinase inhibitor), PD98059 (inhibitor of MEK1,2, an upstream regulator of extracellular-signal regulated kinase) and rapamycin (p70 S6K inhibitor) pointing out that activation of signal transduction pathways unrelated to nVDR is necessary for differentiation. On the other hand, inhibition of cytosolic phospholipase A2 acceler­ated the differentiation of HL-60 cells induced by either 1,25-D3 or by the vitamin D analogs suggesting possible existence of a feedback loop between extracellular-signal regulated kinases and phospholipase A2.
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