Control of human trophoblast function

The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation. Both processes properly occur as a consequence of an intimate dialogue between fetal and maternal tissues, fulfilled by membrane ligands and receptors, as well as by hormone and local factor release. During blastocyst implantation, generation of distinct trophoblast cell types begins, namely the villous and the extravillous trophoblast, the former of which is devoted to fetal-maternal exchanges and the latter binds the placental body to the uterine wall. Physiological placentation is characterized by the invasion of the uterine spiral arteries by extravillous trophoblast cells arising from anchoring villi. Due to this invasion, the arterial structure is replaced by amorphous fibrinoid material and endovascular trophoblastic cells. This transformation establishes a low-resistance, high-capacity perfusion system from the radial arteries to the intervillous space, in which the villous tree is embedded. The physiology of pregnancy depends upon the orderly progress of structural and functional changes of villous and extravillous trophoblast, whereas a derangement of such processes can lead to different types of complications of varying degrees of gravity, including possible pregnancy loss and maternal life-threatening diseases. In this review we describe the mechanisms which regulate trophoblast differentiation, proliferation, migration and invasiveness, and the alterations in these mechanisms which lead to pathological conditions. Furthermore, based on the growing evidence that proper inflammatory changes and oxidative balance are needed for successful gestation, we explain the mechanisms by which agents able to influence such processes may be useful in the prevention and treatment of pregnancy disorders

Somatostatin coupling to adenylyl cyclase activity in the mouse retina

The peptide somatostatin-14 (SRIF) acts in the mammalian retina through its distinct receptors (sst1-5). Scarce information is available on SRIF function in the retina, including the elucidation of transduction pathways mediating SRIF action. We have investigated SRIF and SRIF receptor modulation of adenylyl cyclase (AC) activity in both wild type (WT) retinas and sst1 or sst2 knock-out (KO) retinas which are known to over-express sst2 or sst1 receptors, respectively. In WT retinas, application of SRIF compounds does not affect forskolin-stimulated AC activity. In contrast, activation of sst1 or sst2 receptors inhibits AC in the presence of sst2 or sst1 receptor antagonists, respectively. Results from sst1 KO retinas demonstrate that either SRIF or octreotide, pertussis toxin-dependently inhibit AC activity. In contrast, in sst2 KO retinas, neither SRIF nor CH-275, an sst1 receptor agonist, are found to influence AC activity. As revealed by immunoblotting experiments, in sst1 KO retinas, levels of Goα proteins are 60% higher than in WT retinas and this increase in Goα protein levels is concomitant with an increase in sst2A receptor expression. We conclude that interactions between sst1 and sst2 receptors may prevent SRIF effects on AC activity. In addition, we suggest that the density of sst2 receptors and/or Goα proteins may represent the rate-limiting factor for the sst2 receptor-mediated inhibition of AC.L'articolo è disponibile sul sito dell'editore http://www.springerlink.com

Electron dispersive X-ray spectroscopy and degradation properties of hyaluronic acid decorated microparticles

The purpose of this study was to produce poly(DL-lactic-co-glycolic acid) (PLGA) – based microparticles (MPs), externally decorated with hyaluronic acid (HA). The MPs are intended for intravitreal injections in the treatment of posterior eye segment and have been designed to prolong the release of growth factors into the vitreous body, therefore aiming to increase the time interval between two consecutive injections. The MPs, prepared by a modified double emulsion-solvent evaporation technique and loaded with bovine serum albumins (BSA) and ciliary neurotrophic factor (CNTF), were spherical, with a diameter around 70 μm and a > 90% encapsulation efficiency. Energy Dispersive Spectroscopy (EDS) outcomes indicated that HA presence in the external aqueous phase of the emulsion did affect the surface properties of MPs. Moreover, poloxamers drastically slowed down MP degradation properties which are, in turn, closely related to their ability to prolong drug release. This is promising for the envisaged application of the produced MPs. Further work will be devoted to optimizing MP formulation with respect to the envisaged intravitreal route of administration.The purpose of this study was to produce poly(DL-lactic-co-glycolic acid) (PLGA) - based microparticles (MPs), externally decorated with hyaluronic acid (HA). The MPs are intended for intravitreal injections in the treatment of posterior eye segment and have been designed to prolong the release of growth factors into the vitreous body, therefore aiming to increase the time interval between two consecutive injections. The MPs, prepared by a modified double emulsion-solvent evaporation technique and loaded with bovine serum albumins (BSA) and ciliary neurotrophic factor (CNTF), were spherical, with a diameter around 70 mu m and a > 90% encapsulation efficiency. Energy Dispersive Spectroscopy (EDS) outcomes indicated that HA presence in the external aqueous phase of the emulsion did affect the surface properties of MPs. Moreover, poloxamers drastically slowed down MP degradation properties which are, in turn, closely related to their ability to prolong drug release. This is promising for the envisaged application of the produced MPs. Further work will be devoted to optimizing MP formulation with respect to the envisaged intravitreal route of administration.Peer reviewe

Teenage maternity: life’s new meaning?

Objective: To identify transformations arising from teen pregnancy from the perspective of young women. Method: Study of qualitative and descriptive approach with 34 young women of low socio-economic strata that gave birth in the year 2010 as teenagers. The data have been collected through semistructured interviews with questions about life before and after maternity, explored through content analysis. Results: The life of the teenagers before pregnancy is heterogeneous in social, work and schooling aspects. After maternity, the freedom of being is re-confi gured, bringing losses related to the abandonment of studies, to the reduction in social life and to the stigma of teenage maternity; the gains from resignifi cation of lifestyle, the abandonment of illegal and criminal conduct, increased selfconfi dence the reduction of exposure to violence inside the family, accompanied by new responsibilities, from the reconciliation of study and work or the abandonment of one of these activities. Conclusion: Maternity generates a feeling of satisfaction brought about by the experience of being a mother, with a new social identity

Biological activity of somatostatin receptors in GC rat tumour somatotrophs: evidence with sst1-sst5 receptor-selective nonpeptidyl agonists

The physiological actions of somatostatin-14 (SRIF) receptor subtypes (sst1-sst5), which are endogenously expressed in GC cells, have not yet been elucidated, although there is evidence that sst2 receptors are negatively coupled to cytosolic free Ca2+ concentration ([Ca2+]i) and cAMP accumulation. In addition, both sst1 and sst2 receptors are negatively coupled to growth hormone (GH) secretion in GC cells. Here we report on studies concerning the expression, the pharmacology and the functional role of native SRIF receptors in GC cells with the use of five nonpeptidyl agonists, highly selective for each of the SRIF receptors. Radioligand binding studies show that sst2 and sst5 receptors are present at different relative densities, while the presence of sst3 and sst4 receptors appears to be negligible. The absence of sst1 receptor binding was unexpected in view of sst1 receptor functional effects on GH secretion. This suggests very efficient receptor-effector coupling of a low density population of sst1 receptors. Functionally, only sst2 receptors are coupled to the inhibition of [Ca2+]i and cAMP accumulation and the selective activation of sst5 receptors facilitates the stimulation of adenylyl cyclase activity through Gi/o proteins. This effect was not observed when sst2 and sst5 receptors were simultaneously activated, suggesting that there is a functional interaction between sst2 and sst5 receptors. In addition, sst1, sst2 and sst5 receptor activation inhibits GH release, further indicating that SRIF can modulate GH secretion in GC cells through mechanisms both dependent and independent on [Ca2+]i and cAMP-dependent pathways. The present data suggest SRIF-mediated functional effects in GC cells to be very diverse and provide compelling arguments to propose that multiple native SRIF receptors expressed in the same cells are not simply redundant, but contribute to marked signalling diversity.L'articolo è disponibile sul sito dell'editore http://www.sciencedirect.com

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations