Growth hormone prolongs survival in experimental postinfarction heart failure

AbstractObjectivesWe evaluated the effects of growth hormone (GH) on survival in experimental heart failure (HF).BackgroundGrowth hormone has been beneficial in various models of experimental HF. Whether GH also affects HF progression and survival is not known.MethodsA total of 119 rats with moderate myocardial infarction were randomized to receive either GH (3.5 mg/kg every other day) or placebo for 28 days. Treatment was initiated one month after coronary ligation; the follow-up lasted 13 months. In the surviving animals, Doppler echocardiography and closed-chest Millar left ventricular (LV) catheterization were performed. Apoptosis, collagen volume fraction, and capillary density in the LV zone remote from infarction were measured. The early effects of GH on apoptosis were also assessed in a subgroup of eight infarcted rats, treated as specified earlier and euthanized at one month.ResultsSurvival rate was 68% in GH-treated rats and 48% in the placebo group (p = 0.0377). Growth hormone had no effect on myocardial architecture, systolic function, and sarcoplasmatic reticulum calcium ATPase-2 messenger ribonucleic acid. Growth hormone improved LV relaxation; this was associated with a 50% reduction in collagen volume fraction and a 27% increase in capillary density. Growth hormone reduced the apoptotic index by 50% at one month and by 33% at 13 months.ConclusionsGrowth hormone prolonged survival of rats with postinfarction HF. This effect was associated with marked attenuation of cardiomyocyte apoptosis and pathologic interstitial remodeling in the surviving myocardium and enhanced LV relaxation

Antineoplastic-related cardiotoxicity, morphofunctional aspects in a murine model: contribution of the new tool 2D-speckle tracking

Objective: Considering that global left ventricular systolic radial strain is a sensitive technique for the early detection of left ventricular dysfunction due to antineoplastics and the analysis of segmental myocardial contractility, we evaluated this technique for early detection of trastuzumab-related cardiotoxicity by comparing it with cardiac structural damage. Methods: Groups of six mice were injected with trastuzumab or doxorubicin, used either as single agents or in combination. Cardiac function was evaluated by transthoracic echocardiography measurements before and after treatment for 2 or 7 days, by using a Vevo 2100 high-resolution imaging system. After echocardiography, mice were euthanized, and hearts were processed for histological evaluations, such as cardiac fibrosis, apoptosis, capillary density, and inflammatory response. Results: Trastuzumab-related cardiotoxicity was detected early by 2D strain imaging. Radial strain was reduced after 2 days in mice treated with trastuzumab alone (21.2%±8.0% vs 40.5%±4.8% sham; P<0.01). Similarly, trastuzumab was found to induce apoptosis, capillary density reduction, and inflammatory response in cardiac tissue after 2 days of treatment, in a fashion similar to doxorubicin. On the contrary, fractional shortening reduction and cardiac fibrosis were observed only after 7 days of trastuzumab treatment, in contrast to doxorubicin treatment which induced early fibrosis and fractional shortening reduction. Conclusion: The reduction of left ventricular systolic strain after 2 days of trastuzumab treatment may indicate early myocardial functional damage before the reduction in left ventricular ejection fraction and this early dysfunction is well correlated with structural myocardial damage, such as apoptosis and inflammatory response. Fractional shortening reduction after 7 days of trastuzumab treatment is related to fibrosis in cardiac tissue

Beauveria bassiana rewires molecular mechanisms related to growth and defense in tomato

Plant roots can exploit beneficial associations with soil-inhabiting microbes, promoting growth and expanding the immune capacity of the host plant. In this work, we aimed to provide new information on changes occurring in tomato interacting with the beneficial fungus Beauveria bassiana. The tomato leaf proteome revealed perturbed molecular pathways during the establishment of the plant–fungus relationship. In the early stages of colonization (5–7 d), proteins related to defense responses to the fungus were down-regulated and proteins related to calcium transport were up-regulated. At later time points (12–19 d after colonization), up-regulation of molecular pathways linked to protein/amino acid turnover and to biosynthesis of energy compounds suggests beneficial interaction enhancing plant growth and development. At the later stage, the profile of leaf hormones and related compounds was also investigated, highlighting up-regulation of those related to plant growth and defense. Finally, B. bassiana colonization was found to improve plant resistance to Botrytis cinerea, impacting plant oxidative damage. Overall, our findings further expand current knowledge on the possible mechanisms underlying the beneficial role of B. bassiana in tomato plants

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

Production of an oxytocin like substance by the subcommissural organ (SCO), related to the reproductive cycle in oviparous and viviparous reptiles.

The subcommissural organ (SCO) is a circumventricular organ of glial origin typical of all vertebrates, The SCO releases its secretion into the third ventricle to constitute Reissner's fibre (RF). Reportedly, in reptiles, SCO has cyclic secretory activity related to the reproductive cycle, In this immunocytochemical study we show that, in females of oviparous reptiles (Lacertidae: Podarcis sicula) and in a viviparous species (Scincidae: Chalcides chalcides), SCO secretion consists of hormones, in part of the oxytocin-like (OXY-like) type. The amount of OXY-like material in the cells and in the third ventricle varies according to the different stages of the reproductive cycle. In the oviparous species, OXY-like hormone secretion can be induced by FSH administration at 28 degrees C, in the period of winter reproductive stasis as well, In the viviparous skink, showing an annual single ovulatory cycle, OXY-like secretion is present in the basal region of the cells, and is released into the third ventricle only at delivery, The role of an OXY-like hormone in the SCO is here discussed in relation to the different stages of the reproductive cycle. Its influence on the hypothalamus-hypophysis-gonad axis and its role in the transport of eggs into the ducts in the oviparous species, and at delivery in the viviparous one, are also suggested

[The role of aldosterone in the development of postinfarction fibrosis]

Aldosterone was discovered in 1953, and until the beginning of the 1960s, when spironolactone was developed, it was the focus of considerable interest among the scientific community. The following 30 years represented a sort of Dark Age, interrupted by the Weber's classic studies. He first demonstrated the pivotal role of aldosterone in the promotion of cardiac hypertrophy and fibrosis and such an observation represented a solid background for the implementation of large survival trials, the RALES and the EPHESUS. These landmark studies showed that aldosterone receptor blockade prolongs survival in advanced and postinfarction heart failure, respectively. After a myocardial infarction, there is a significant upregulation of the local steroidogenic system in the area remote from the scar, that leads to a remarkable fibroblast activation, collagen deposition, and reactive fibrosis. Fibrosis in turn further impairs systolic and diastolic function, and induces electrical heterogeneity with attendant ominous arrhythmias. The following review will dwell upon the importance of fibrosis in postinfarction heart failure, the role of aldosterone, and the novel therapeutic approach based on mineralocorticoid receptor blockade