Dynorphin induced magnetic ordering in lipid bilayers as studied by 31P NMR spectroscopy

AbstractLipid bilayers of dimyristoyl phosphatidylcholine (DMPC) containing opioid peptide dynorphin A(1–17) are found to be spontaneously aligned to the applied magnetic field near at the phase transition temperature between the gel and liquid crystalline states (Tm=24°C), as examined by 31P NMR spectroscopy. The specific interaction between the peptide and lipid bilayer leading to this property was also examined by optical microscopy, light scattering, and potassium ion-selective electrode, together with a comparative study on dynorphin A(1–13). A substantial change in the light scattering intensity was noted for DMPC containing dynorphin A(1–17) near at Tm but not for the system containing A(1–13). Besides, reversible change in morphology of bilayer, from small lipid particles to large vesicles, was observed by optical microscope at Tm. These results indicate that lysis and fusion of the lipid bilayers are induced by the presence of dynorphin A(1–17). It turned out that the bilayers are spontaneously aligned to the magnetic field above Tm in parallel with the bilayer surface, because a single 31P NMR signal appeared at the perpendicular position of the 31P chemical shift tensor. In contrast, no such magnetic ordering was noted for DMPC bilayers containing dynorphin A(1–13). It was proved that DMPC bilayer in the presence of dynorphin A(1–17) forms vesicles above Tm, because leakage of potassium ion from the lipid bilayers was observed by potassium ion-selective electrode after adding Triton X-100. It is concluded that DMPC bilayer consists of elongated vesicles with the long axis parallel to the magnetic field, together with the data of microscopic observation of cylindrical shape of the vesicles. Further, the long axis is found to be at least five times longer than the short axis of the elongated vesicles in view of simulated 31P NMR lineshape

Hygroscopic dilators vs balloon catheter ripening of the cervix for induction of labor in nulliparous women at term: Retrospective study.

To compare the efficacy and safety of hygroscopic dilators and balloon catheters for ripening of the cervix in induction of labor.This retrospective, observational study used data from the Successive Pregnancy Birth Registry System of the Japan Society of Obstetrics and Gynecology from 2012 to 2014. Nulliparous women in whom labor was induced by mechanical methods of cervical ripening at term were enrolled. The eligible women were divided into dilator, balloon 0.05). The vaginal instrumental delivery rate was higher in the two-balloon groups than in the dilator group. The volume of intrapartum hemorrhage was lowest in the dilator group. No significant difference in the frequencies of uterine rupture and intrauterine infection were observed among the dilator and two-balloon groups. With regard to neonatal outcomes, the frequency of a low Apgar score was statistically significantly lower in the dilator group than in the two-balloon groups. Moreover, the frequency of neonatal death tended to be lower in the dilator group than in the two-balloon groups.With regard to cervical ripening for labor induction in nulliparous women at term, the vaginal delivery rate on using a dilator and on using a balloon seems to be equivalent. Concerning maternal complications and neonatal outcomes, cervical ripening with hygroscopic dilators in labor induction might be safer

Delivery outcome.

<p>Delivery outcome.</p

A multicenter, single-arm, phase II clinical trial of adrenomedullin in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of hereditary cerebral small vessel disease (SVD), currently lacks disease-modifying treatments. Adrenomedullin (AM), a vasoactive peptide with angiogenic, vasodilatory, anti-inflammatory, and anti-oxidative properties, shows potential effects on the neuro-glial-vascular unit. Objective: The AdrenoMedullin for CADASIL (AMCAD) study aims to assess the efficacy and safety of AM in patients with CADASIL. Sample size: Overall, 60 patients will be recruited. Methods: The AMCAD is a multicenter, investigator-initiated, single-arm phase II trial. Patients with a confirmed CADASIL diagnosis, based on NOTCH3 genetic testing, will receive an 8-h AM treatment (15 ng/kg/min) for 14 days following a baseline assessment (from day 1 to day 14). Follow-up evaluations will be performed on days 15, 28, 90, and 180. Study outcomes: The primary endpoint is the cerebral blood flow change rate in the frontal cortex, evaluated using arterial spin labeling magnetic resonance imaging, from baseline to day 28. Summary statistics, 95% confidence intervals, and a one-sample t-test will be used for analysis. Conclusion: The AMCAD study aims to represent the therapeutic potential of AM in patients with CADASIL, addressing an unmet medical need in this challenging condition. Clinical Trial Registration: jRCT 2,051,210,117 (https://jrct.niph.go.jp/en-latest-detail/jRCT2051210117)