Plasma active and inactive renin and fetal complications in women with high risk pregnancies.

To examine whether the activation of the renin system, which occurs during pregnancy, may be relevant for the development and the outcome of the fetus, we measured active and inactive renin throughout gestation in 29 women having a pregnancy defined as "high risk" because of a clinical history of hypertension, nephropathy, and unexplained abortions. In 23 of these women who delivered full-term infants with normal weight and status, we found that active renin increased progressively from early pregnancy until the end of the second trimester and then declined slightly thereafter. In contrast, in the remaining six women who had fetal complications consisting of either signs of distress requiring cesarean section or growth retardation, the increase in active renin failed to occur. In all women the levels of inactive renin were more elevated throughout gestation than those observed in nonpregnant women, and were higher, although not significantly, in women without fetal complications than in those with fetal complications. Thus, a blunted activation of the renin system during pregnancy is associated with alteration in fetal development and may possibly contribute to it.     

Evaluation of the circadian profile of peripheral plasma galanin concentrations in normal subjects

Galanin administration can influence pituitary function principally resulting in an increase in GH secretion. However, the role of circulating GAL levels in human endocrine function is still unknown. In the present study we simultaneously measured the circadian profiles of GAL, ACTH and GH in peripheral blood of ten adult subjects. Plasma samples were collected through an intravenous catheter at 0800, 1200, 1600, 2000, 2200, 2400, 0200, 0400 hours. The results were statistically evaluated by the cosinor analysis technique. A significant circadian rhythm of both plasma ACTH (p < 0.001) and GH levels (p < 0.03) was found with acrophases occurring at 0753 hrs and 0131 hrs for ACTH and GH, respectively. On the contrary, no significant rhythm was found in plasma GAL levels, indicating that no correlations exist between GAL and either GH or ACTH circadian profiles. Furthermore, the simultaneous assay of both GAL and GH plasma levels during a nocturnal frequent sampling performed in four volunteers showed the presence of peaks in GAL levels which, however, were not concomitant to the peaks in GH levels. These data demonstrate the lack of rhythmicity in the circadian profile of plasma GAL levels in healthy human subjects. The role of GAL in human endocrine function remains unknown and these results suggest that, in spite of the well documented increase in plasma GH concentrations following the intravenous administration of GAL, physiologically circulating levels of GAL are likely not involved in the regulation of GH secretion.     

Activation of Haem-Oxidized Soluble Guanylyl Cyclase with BAY 60-2770 in Human Platelets Lead to Overstimulation of the Cyclic GMP Signaling Pathway

Background and Aims

Nitric oxide-independent soluble guanylyl cyclase (sGC) activators reactivate the haem-oxidized enzyme in vascular diseases. This study was undertaken to investigate the anti-platelet mechanisms of the haem-independent sGC activator BAY 60-2770 in human washed platelets. The hypothesis that sGC oxidation potentiates the anti-platelet activities of BAY 60-2770 has been tested.

Methods

Human washed platelet aggregation and adhesion assays, as well as flow cytometry for α_IIbβ₃ integrin activation and Western blot for α1 and β1 sGC subunits were performed. Intracellular calcium levels were monitored in platelets loaded with a fluorogenic calcium-binding dye (FluoForte).

Results

BAY 60-2770 (0.001–10 µM) produced significant inhibition of collagen (2 µg/ml)- and thrombin (0.1 U/ml)-induced platelet aggregation that was markedly potentiated by the sGC inhibitor ODQ (10 µM). In fibrinogen-coated plates, BAY 60-2770 significantly inhibited platelet adhesion, an effect potentiated by ODQ. BAY 60-2770 increased the cGMP levels and reduced the intracellular Ca²⁺ levels, both of which were potentiated by ODQ. The cell-permeable cGMP analogue 8-Br-cGMP (100 µM) inhibited platelet aggregation and Ca²⁺ levels in an ODQ-insensitive manner. The cAMP levels remained unchanged by BAY 60-2770. Collagen- and thrombin-induced α_IIbβ₃ activation was markedly inhibited by BAY 60-2770 that was further inhibited by ODQ. The effects of sodium nitroprusside (3 µM) were all prevented by ODQ. Incubation with ODQ (10 µM) significantly reduced the protein levels of α1 and β1 sGC subunits, which were prevented by BAY 60-2770.

Conclusion

The inhibitory effects of BAY 60-2770 on aggregation, adhesion, intracellular Ca²⁺ levels and α_IIbβ₃ activation are all potentiated in haem-oxidizing conditions. BAY 60-2770 prevents ODQ-induced decrease in sGC protein levels. BAY 60-2770 could be of therapeutic interest in cardiovascular diseases associated with thrombotic complications.     

Contribution to the genetics of the serum β-lipoproteins in man

Summary A study on the possible existence of association and linkage of the Ag(x,y,a₁) system with ABO, MNSs, Pp, Rhesus, Kell, Duffy, Gm, Inv, Hp, and Gc groups is presented. No evidence of association and linkage was found.     

Contribution to the genetics of serum β-lipoprotein in man

Summary The study of some families of the double black cross type confirmed complete linkage of theAg ^x/y , andAg ^c/g loci.

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Zusammenfassung An Hand einer Untersuchung einiger Familien vom double back cross-Typ konnte das komplette linkage der Gen-LociAg ^x/y , undAg ^c/g bestätigt werden.

     

Climate determinants of breeding and wintering ranges of lesser kestrels in Italy and predicted impacts of climate change

Climate warming would theoretically create conditions for the breeding range expansion of pseudo‐steppe Mediterranean and long‐distance migrant species and provide the possibility for these to overwinter in the same breeding areas. However, contemporary changes in rainfall regimes might have negative effects on the climate suitability and in turn, shrink species potential range. The lesser kestrel Falco naumanni is highly sensitive to rainfall oscillations and has recently extended its Italian breeding range towards northern latitudes and increasing its wintering records. We modelled the effects of temperature and rainfall on current and future climate suitability for lesser kestrels in both the breeding and wintering periods by using MaxEnt. Models were based on the distribution of 298 colonies and 40 wintering records. Future climate suitability was assessed under eight different scenarios. Spring rainfall amount resulted as the main determinant of breeding climate suitability, so its predicted reduction will determine a shrinkage in suitable areas (–42.10% in 2050; –32.07% in 2070). Specifically, the 66.05% of Italian colonies will be outside the climatically suitable area by 2050. However wide areas, suitable under current climate conditions, are still not occupied by lesser kestrel and allow the potential expansion of its Italian breeding range in the short term. Temperature seasonality mainly determined the species’ winter climate suitability, which is overall predicted to boost in the next decades (+145.03% in 2050; and +123.91% in 2070). All but one future scenarios predicted a northward shift of about 40 km for both breeding and wintering climate suitability. Despite its recent expansion, we have found that climate change will pose conservation concerns for the Italian breeding population of lesser kestrels. Indeed, changes in non‐climate factors will also outline the future suitability of the Italian range for lesser kestrels in both seasons with effects that might both strengthen or mitigate climate effects.