Gonadorelin Acetate

We aimed to evaluate the effects of administering estradiol (E-17β) at the moment of timed-AI (TAI) on uterine gene expression, estrous expression rate (EER), and pregnancy rate (P/TAI) in Nelore cows with a small dominant follicle (DF) or not showing estrus at TAI. In Experiments 1 and 2 (Exp1, Exp2) cows were submitted to a P4/E-17β-based protocol (day 0) for synchronization of ovulation. On day 7, devices were removed, cows received 1 mg E-17β cypionate and 12.5 mg dinoprost. On day 9, cows with DF < 11.5 mm in diameter were split into different groups. In Exp1 (n = 16/group): Control (no treatment), E-2 (2 mg E-17β) and E-4 (4 mg E-17β). In Exp2: Control (n = 12); E-2 (n = 14); GnRH (0.1 mg gonadorelin acetate, n = 13); and E-2+GnRH (association of GnRH and E-17β, n = 13). Between days 9 and 11, endometrial thickness (ET), time of ovulation detection, and EER were recorded. In Exp1, a uterine cytological sample was collected 4 h after treatment to evaluate the transcript expression of receptors for E-17β (ESR1 and ESR2), oxytocin (OXTR), and P4 (PGR). In Experiment 3 (Exp3), 3829 suckled cows were submitted to a P4/E-17β-based protocol for TAI. On day 9, devices were removed and cows received 1 mg E-17β cypionate and 0.4 mg sodium cloprostenol. On day 11, TAI was performed and cows that did not demonstrate estrus received 0.1 mg gonadorelin acetate, and were allocated into two groups: GnRH (n = 368) and E-2+GnRH (2 mg E-17β; n = 363). In Exp1, plasma E-17β concentrations increased at 4 h after treatment in a dose-dependent manner but reduced at 12 h. The E-17β-treated cows had greater transcript abundance for OXTR and lesser for ESR1 and ESR2, and the ET was reduced 12 h after treatment (P < 0.05). No significant difference (P > 0.1) was observed between the E-17β doses in estrus or ovulation rate. In Exp2, the interval from treatment to ovulation was longer (P < 0.05) in the E-17β group. GnRH-treated cows showed higher ovulation rates (89 vs. 35 %) compared to cows not treated with GnRH, as E-17β-treated cows (P < 0.01) had a lower ovulation rate compared to those not receiving E-17β (44 vs. 78 %). In Exp3, P/TAI was 55 % for cows in estrus. For those not showing estrus, no difference (P > 0.1) in P/TAI was observed between GnRH (34 %) and E-2+GnRH (31 %) groups. Cows with a DF ≥ 11 mm (n = 192) had a greater (P < 0.05) P/TAI (49 %) than those with DF < 11 mm (n = 377; 29 %). In conclusion, E-17β administration in the moment of TAI modulates the mRNA expression of uterine receptors in cows with a small DF but does not impact the P/TAI compared with GnRH treatment in suckled Nelore not showing estrus previous to TAI.

Pulmonary lymphangitis carcinomatosis is generally characterized by resistance to chemotherapy and is associated with a poor prognosis. Herein, we present a case of pulmonary lymphangitic carcinomatosis from recurrent breast cancer that responded well to trastuzumab deruxtecan(T-DXd). The patient was a 40-year-old woman with hormone receptor-positive, HER2-positive breast cancer. At the age of 31, she had undergone a left mastectomy with axillary lymph node dissection. She received adjuvant chemotherapy(5-fluorouracil-epirubicin-cyclophosphamide, docetaxel, and trastuzumab)followed by endocrine therapy(tamoxifen and LH-RHa). Three years after the surgery, pulmonary and bone metastases were detected and she was treated with trastuzumab, pertuzumab, and capecitabine. Liver metastases were detected, and she was treated with trastuzumab emtansine. Nine years after surgery, the patient developed dyspnea and was diagnosed with lymphangitis carcinomatosis. After initiating T-DXd, dyspnea rapidly improved, and ground glass opacity on CT scan disappeared. She responded well to the treatment, with prolonged, stable disease for 1 year and 2 months. Thus, T-DXd may be effective against pulmonary lymphangitis carcinomatosis, which is generally characterized by resistance to chemotherapy.