EUS is the most effective technique used in the diagnosis of pancreatic cancer, the present study demonstrating an accuracy of 92.7%. Moreover, EUS offers the possibility to collect samples for cytological examination by EUS guided fine needle aspiration. However, there are some limitations of EUS in identifying extra-abdominal metastases. Thus, the assessment of tumor extension must be completing by performing CT or MRI.

G protein-coupled estrogen receptor 1 (GPER), also named GPR30, has been previously identified in the female reproductive system. In this study, GPER expression was found in the female rat myometrium by reverse transcriptase-polymerase chain reaction and immunocytochemistry. Using GPER-selective ligands, we assessed the effects of the GPER activation on resting membrane potential and cytosolic Ca²⁺ concentration ([Ca²⁺]_i) in rat myometrial cells, as well as on contractility of rat uterine strips. G-1, a specific GPER agonist, induced a concentration-dependent depolarization and increase in [Ca²⁺]_i in myometrial cells. The depolarization was abolished in Na⁺-free saline. G-1-induced [Ca²⁺]_i increase was markedly decreased by nifedipine, a L-type Ca²⁺ channel blocker, by Ca²⁺-free or Na⁺-free saline. Intracellular administration of G-1 produced a faster and transitory increase in [Ca²⁺]_i, with a higher amplitude than that induced by extracellular application, supporting an intracellular localization of the functional GPER in myometrial cells. Depletion of internal Ca²⁺ stores with thapsigargin produced a robust store-activated Ca²⁺ entry; the Ca²⁺ response to G-1 was similar to the constitutive Ca²⁺ entry and did not seem to involve store-operated Ca²⁺ entry. In rat uterine strips, administration of G-1 increased the frequency and amplitude of contractions and the area under the contractility curve. The effects of G-1 on membrane potential, [Ca²⁺]_i, and uterine contractility were prevented by pretreatment with G-15, a GPER antagonist, further supporting the involvement of GPER in these responses. Taken together, our results indicate that GPER is expressed and functional in rat myometrium. GPER activation produces depolarization, elevates [Ca²⁺]_i and increases contractility in myometrial cells.

Nesfatin‐1, a peptide whose receptor is yet to be identified, has been involved in the modulation of feeding, stress, and metabolic responses. More recently, increasing evidence supports a modulatory role for nesfatin‐1 in autonomic and cardiovascular activity. This study was undertaken to test if the expression of nesfatin‐1 in the nucleus ambiguus, a key site for parasympathetic cardiac control, may be correlated with a functional role. As we have previously demonstrated that nesfatin‐1 elicits Ca²⁺ signaling in hypothalamic neurons, we first assessed the effect of this peptide on cytosolic Ca²⁺ in cardiac pre‐ganglionic neurons of nucleus ambiguus. We provide evidence that nesfatin‐1 increases cytosolic Ca²⁺ concentration via a Gi/o‐coupled mechanism. The nesfatin‐1‐induced Ca²⁺ rise is critically dependent on Ca²⁺ influx via P/Q‐type voltage‐activated Ca²⁺ channels. Repeated administration of nesfatin‐1 leads to tachyphylaxis. Furthermore, nesfatin‐1 produces a dose‐dependent depolarization of cardiac vagal neurons via a Gi/o‐coupled mechanism. In vivo studies, using telemetric and tail‐cuff monitoring of heart rate and blood pressure, indicate that microinjection of nesfatin‐1 into the nucleus ambiguus produces bradycardia not accompanied by a change in blood pressure in conscious rats. Taken together, our results identify for the first time that nesfatin‐1 decreases heart rate by activating cardiac vagal neurons of nucleus ambiguus. image Our results indicate that nesfatin‐1, one of the most potent feeding peptides, increases cytosolic Ca²⁺ by promoting Ca²⁺ influx via P/Q channels and depolarizes nucleus ambiguus neurons; both effects are Gi/o‐mediated. In vivo studies indicate that microinjection of nesfatin‐1 into nucleus ambiguus produces bradycardia in conscious rats. This is the first report that nesfatin‐1 increases the parasympathetic cardiac tone.

Magnesium sulfate, mainly used in obstetrics to treat eclamptic convulsions, is currently questioned as to its clinical tocolytic effect. We aimed to study the relaxant action (if any) of magnesium sulfate on in vitro pregnant and non-pregnant myometrium. Myometrial strips, harvested from five pregnant women (35-39 gestational weeks) during Cesarean procedures indicated for dystocia or scared uterus and five non-pregnant women during hysterectomy or myomectomy for benign conditions, were placed in a Krebs-Henseleit solution organ bath and the isometric force was registered. We assessed the effect of Mg2+ (magnesium sulfate) at different concentrations (0.50-10 mM) on spontaneous and oxytocin-induced (1 microM) myometrial contractility. Mg2+ temporarily reduced spontaneous myometrial contractions in a dose-dependent manner, with efficient regimens at 2.0-2.5 mM, and arrested contractility completely at 3 mM. Oxytocin-induced contractions were reduced by 30-40% at 8 mM and decreased further at 9-10 mM. Induced contractions were reduced, in a dose-dependent and time-dependent manner (maximum effect at 20 min), at higher Mg2+ concentrations and with non-significant proportional differences between pregnant and non-pregnant myometrium. The present in vitro study suggests a possible benefit of Mg2+ in the inhibition of spontaneous myometrial contractility, but not of uterine-induced hyperactivity.

Angiotensin II is a modulator of myometrial activity; both AT₁and AT₂receptors are expressed in myometrium. Since in other tissues angiotensin II has been reported to activate intracellular receptors, we assessed the effects of intracellular administration of angiotensin II via microinjection on myometrium, using calcium imaging. Intracellular injection of angiotensin II increased cytosolic Ca²⁺concentration ([Ca²⁺]_i) in myometrial cells in a dose-dependent manner. The effect was abolished by the AT₁receptor antagonist losartan but not by the AT₂receptor antagonist PD-123319. Disruption of the endo-lysosomal system, but not that of Golgi apparatus, prevented the angiotensin II-induced increase in [Ca²⁺]_i. Blockade of AT₁receptor internalization had no effect, whereas blockade of microautophagy abolished the increase in [Ca²⁺]_iproduced by intracellular injection of angiotensin II; this indicates that microautophagy is a critical step in transporting the peptide into the endo-lysosomes lumenum. The response to angiotensin II was slightly reduced in Ca²⁺-free saline, indicating a major involvement of Ca²⁺release from internal stores. Blockade of inositol 1,4,5-trisphosphate (IP₃) receptors with heparin and xestospongin C or inhibition of phospholipase C (PLC) with U-73122 abolished the response to angiotensin II, supporting the involvement of PLC-IP₃pathway. Angiotensin II-induced increase in [Ca²⁺]_iwas slightly reduced by antagonism of ryanodine receptors. Taken together, our results indicate for the first time that in myometrial cells, intracellular angiotensin II activates AT₁-like receptors on lysosomes and activates PLC-IP₃-dependent Ca²⁺release from endoplasmic reticulum; the response is further augmented by a Ca²⁺-induced Ca²⁺release mechanism via ryanodine receptors activation.