Orally available Mn porphyrins with superoxide dismutase and catalase activities

Superoxide dismutase/catalase mimetics, such as salen Mn complexes and certain metalloporphyrins, catalytically neutralize reactive oxygen and nitrogen species, which have been implicated in the pathogenesis of many serious diseases. Both classes of mimetic are protective in animal models of oxidative stress. However, only AEOL11207 and EUK-418, two uncharged Mn porphyrins, have been shown to be orally bioavailable. In this study, EUK-418 and several new analogs (the EUK-400 series) were synthesized and shown to exhibit superoxide dismutase, catalase, and peroxidase activities in vitro. Some also protected PC12 cells against staurosporine-induced cell death. All EUK-400 compounds were stable in simulated gastric fluid, and most were substantially more lipophilic than the salen Mn complexes EUK-189 and EUK-207, which lack oral activity. Pharmacokinetics studies demonstrate the presence of all EUK-400 series compounds in the plasma of rats after oral administration. These EUK-400 series compounds are potential oral therapeutic agents for cellular damage caused by oxidative stress

Model Risk Management. Le prassi e il modello a tendere.

I modelli hanno assunto un ruolo pervasivo nell’operatività bancaria configurandosi come driver essenziali nel decision making sia in ambito regolamentare che gestionale, e questa considerazione, seppur con caratterizzazioni diverse, risulta valida sia per banche “significant” che “less significant”. Si evidenzia che il numero e la complessità dei modelli hanno raggiunto un livello di ampiezza tale da richiederne una gestione dedicata e strumenti specifici per evitare che la base decisionale si poggi su algoritmi, dati o elaborazioni non adeguati. Oltre alla complessità intrinseca dei modelli, si aggiunge una crescente interconnessione tra gli stessi per cui le criticità di un modello possono riverberarsi sui modelli collegati con effetti poco prevedibili. Le mutevoli condizioni di contesto (accentuate dall’emergenza Covid), hanno ulteriormente amplificato l’esigenza di ridurre la distanza tra l’identificazione delle criticità sui modelli, la presa in carico delle azioni correttive, il relativo monitoraggio e il rilascio degli interventi. Una catena di trasmissione non adeguata comporta inevitabilmente tempi di risposta più lunghi, con modelli che non sono in grado di rappresentare adeguatamente il contesto operativo

Predicting default probabilities and implementing trading strategies for emerging markets bond portfolios

In this paper we address two main issues: the computation of default probability implicit in emerging markets bond prices and the impact on portfolio risks and returns of expected changes in default probability. Using a reduced-form model, weekly estimates of default probabilities for US Dollar denominated Global bonds of twelve emerging markets are extrapolated for the sample period 1997-2001. The estimation of a logit type econometric model shows that weekly changes of the default probabilities can be explained by means of some capital markets factors. Recursively estimating the logit model using rolling windows of data, out-of-sample forecasts for the dynamics of default probabilities are generated and used to form portfolios of bonds. The practical application provides interesting results, both in terms of testing the ability of a naive trading strategy based on model forecasts to outperform a \u201dcustomized benchmark\u201d, and in terms of the model ability to actively manage the portfolio risk (evaluated in terms of VaR) with respect to a constant proportion allocation

Electrokinetic remediation(EKR) effects under linear and radial electric field at laboratory scale

The remediation of polluted soils by heavy metals concerns wide areas of the planet, and the electrokinetic remediation (EKR) is an alternative method to the traditional ones. Moreover, in the current technologies this technique requests high power levels, with consequent security and cost problems. To enhance the process it is possible to use hydro-silica layers properties: these layers allow to move the heavy metals, if the electrical field is applied for a long time (T > 24 hours). Previous experiences showed that a sinusoidal waveform can improve the efficiency of the process up to 70%. In this paper we show the results of the EKR experiments carried out with two different electric fields: linear and radial. The electric field was controlled both as gradient and waveform (positive sinusoidal and DC). We worked with saturated sands polluted by Cr(VI). The process was monitored and calibrated using sets of voltage electrodes, chemical analysis and complex electrical resistivity of selected sand samples. The EKR process moved the 69% of Cr(VI) applying a linear electric field, while it moved the 34% of Cr(VI), applying a radial electric field. We also observed that the local electric resistivity is an efficient and economic index of the process, and the behaviour of the resistivity versus voltage let us presume that a positive ramp up signal, with a period of 12 hours, should be more effective than the positive sinusoidal one. Moreover, these experiments show that the process electrodeposits the heavy metal on to the surface of the high current electrode, consequently the polarity inversion of the applied electric field can clean this electrode and restore his “storage capacity

Defective AMH signaling disrupts GnRH neuron development and function and contributes to hypogonadotropic hypogonadism.

Congenital hypogonadotropic hypogonadism (CHH) is a condition characterized by absent puberty and infertility due to gonadotropin releasing hormone (GnRH) deficiency, which is often associated with anosmia (Kallmann syndrome, KS). We identified loss-of-function heterozygous mutations in anti-Müllerian hormone (AMH) and its receptor, AMHR2, in 3% of CHH probands using whole-exome sequencing. We showed that during embryonic development, AMH is expressed in migratory GnRH neurons in both mouse and human fetuses and unconvered a novel function of AMH as a pro-motility factor for GnRH neurons. Pathohistological analysis of Amhr2-deficient mice showed abnormal development of the peripheral olfactory system and defective embryonic migration of the neuroendocrine GnRH cells to the basal forebrain, which results in reduced fertility in adults. Our findings highlight a novel role for AMH in the development and function of GnRH neurons and indicate that AMH signaling insufficiency contributes to the pathogenesis of CHH in humans

Doença de Mondor: achados mamográficos e ultra-sonográficos Mondor's disease: mammography and ultrasound findings

A doença de Mondor da mama é uma tromboflebite superficial da mama que se apresenta como um cordão fibroso e espessado na região subcutânea da mama. É uma enfermidade rara, benigna e autolimitada que apresenta dor e retração da pele no nível do vaso afetado. Neste trabalho relatamos dois casos mostrando os achados mamográficos (caso 1) e ultra-sonográficos (caso 2) típicos desta anomalia.<br>Mondor's disease of the breast is a superficial thrombophlebitis of the veins of the breast characterized by the appearance of a thickened fibrotic cord in the subcutaneous tissue. This is a rare, benign and self-limited disease, which presents with pain and skin retraction at the site of the affected vase. We report two cases of patients with Mondor's disease and show the typical mammography (case 1) and ultrasound (case 2) findings