Dock10 Regulates Cardiac Function under Neurohormonal Stress.

Dedicator of cytokinesis 10 (Dock10) is a guanine nucleotide exchange factor for Cdc42 and Rac1 that regulates the JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase) signaling cascades. In this study, we characterized the roles of Dock10 in the myocardium. In vitro: we ablated Dock10 in neonatal mouse floxed Dock10 cardiomyocytes (NMCMs) and cardiofibroblasts (NMCFs) by transduction with an adenovirus expressing Cre-recombinase. In vivo, we studied mice in which the Dock10 gene was constitutively and globally deleted (Dock10 KO) and mice with cardiac myocyte-specific Dock10 KO (Dock10 CKO) at baseline and in response to two weeks of Angiotensin II (Ang II) infusion. In vitro, Dock10 ablation differentially inhibited the α-adrenergic stimulation of p38 and JNK in NMCM and NMCF, respectively. In vivo, the stimulation of both signaling pathways was markedly attenuated in the heart. The Dock10 KO mice had normal body weight and cardiac size. However, echocardiography revealed mildly reduced systolic function, and IonOptix recordings demonstrated reduced contractility and elevated diastolic calcium levels in isolated cardiomyocytes. Remarkably, Dock10 KO, but not Dock10 CKO, exaggerated the pathological response to Ang II infusion. These data suggest that Dock10 regulates cardiac stress-related signaling. Although Dock10 can regulate MAPK signaling in both cardiomyocytes and cardiofibroblasts, the inhibition of pathological cardiac remodeling is not apparently due to the Dock10 signaling in the cardiomyocyte.

Tubal superfetation following frozen-thawed single-embryo transfers in two separate cycles: Case report and literature review.

Superfetation is a very rare occurrence. In the context of assisted reproduction, it has been reported only as an intrauterine pregnancy after ovarian stimulation and/or embryo transfer in the presence of an undiagnosed ectopic pregnancy. Here we report a case of a 27-year-old anovulatory patient, gravida 1 para 1, who underwent two frozen-thawed single-blastocyst transfers in separate cycles. The patient reported that 12 days after the first transfer, she had menstrual bleeding and stopped her estradiol and progesterone supplementation without undergoing a blood human chorionic gonadotropin (ßhCG) test. At her request, a second cycle was immediately initiated, with endometrial thickness measuring 4 mm. Eleven days after the second transfer, the ßhCG value was inappropriately high. A right tubal pregnancy corresponding to 8 gestational weeks was diagnosed. Laparoscopy revealed a prominent right tubal pregnancy in addition to a significantly smaller left tubal pregnancy. The discordant tubal pregnancies were confirmed histologically. To our knowledge, superfetation involving a second ectopic pregnancy coexistent with a first, contralateral ectopic pregnancy consequent to consecutive in vitro fertilization procedures has not previously been described in the medical literature. This case emphasizes the importance of routine ßhCG testing after every IVF cycle, even if apparently unsuccessful.