Autophagy-mediated neuroprotection induced by octreotide in an ex vivo model of early diabetic retinopathy

Neuronal injury plays a major role in diabetic retinopathy (DR). Our hypothesis was that the balance between neuronal death and survival may depend on a similar equilibrium between apoptosis and autophagy and that a neuroprotectant may act by influencing this equilibrium. Ex vivo mouse retinal explants were treated with high glucose (HG) for 10days and the somatostatin analog octreotide (OCT) was used as a neuroprotectant. Chloroquine (CQ) was used as an autophagy inhibitor. Apoptotic and autophagic markers were evaluated using western blot and immunohistochemistry. HG-treated explants displayed a significant increase of apoptosis paralleled by a significant decrease of the autophagic flux, which was likely to be due to increased activity of the autophagy regulator mTOR (mammalian target of rapamycin). Treatment with OCT rescued HG-treated retinal explants from apoptosis and determined an increase of autophagic activity with concomitant mTOR inhibition. Blocking the autophagic flux with CQ completely abolished the anti-apoptotic effect of OCT. Immunohistochemical observations showed that OCT-induced autophagy is localized to populations of bipolar and amacrine cells and to ganglion cells. These observations revealed the antithetic role of apoptosis and autophagy, highlighting their equilibrium from which neuronal survival is likely to depend. These data suggest the crucial role covered by autophagy, which could be considered as a molecular target for DR neuroprotective treatment strategies

Laparotomic vs laparoscopic ovariectomy: comparing the two methods. The ovariectomy in the bitch in laparoscopic era

BACKGROUND: The aim of the present work is to evaluate the effectiveness of the use of ultrasound scalpel during laparoscopic ovariectomy in the bitch. METHODS: Two groups of 10 subjects each, of different races and ages, were compared. In the first group, ovariectomy was performed laparoscopically, using harmonic scalpel to remove ovary. In the second group surgery was performed by means of classical laparotomy. RESULTS: Pre-operative time was similar in both groups. Total operative time, from incision to skin suture, showed significant difference between the two groups, being laparoscopy faster than laparotomy. Partial operative time for bilateral oophorectomy resulted lower using open technique, but, considering each ovary, there was no significant difference in both groups. CONCLUSIONS: The use of harmonic scalpel to perform ovariectomy during laparoscopy is an effective time-sparing surgical approach compared to the already great practicality of laparotomy

Phosphorylated cofilin-2 is more prone to oxidative modifications on Cys39 and favors amyloid fibril formation

Cofilins are small protein of the actin depolymerizing family. Actin polymerization/depolymerization is central to a number of critical cellular physiological tasks making cofilin a key protein for several physiological functions of the cell. Cofilin activity is mainly regulated by phosphorylation on serine residue 3 making this post-translational modification key to the regulation of myofilament integrity. In fact, in this form, the protein segregates in myocardial aggregates in human idiopathic dilated cardiomyopathy. Since myofilament network is an early target of oxidative stress we investigated the molecular changes induced by oxidation on cofilin isoforms and their interplay with the protein phosphorylation state to get insight on whether/how those changes may predispose to early protein aggregation. Using different and complementary approaches we characterized the aggregation properties of cofilin-2 and its phosphomimetic variant (S3D) in response to oxidative stress in silico, in vitro and on isolated cardiomyocytes. We found that the phosphorylated (inactive) form of cofilin-2 is mechanistically linked to the formation of an extended network of fibrillar structures induced by oxidative stress via the formation of a disulfide bond between Cys39 and Cys80. Such phosphorylation-dependent effect is likely controlled by changes in the hydrogen bonding network involving Cys39. We found that the sulfide ion inhibits the formation of such structures. This might represent the mechanism for the protective effect of the therapeutic agent Na2S on ischemic injury

Intra-articular administration of lidocaine plus adrenaline in dogs : pharmacokinetic profile and evaluation of toxicity in vivo and in vitro

The aim of this study was to evaluate the safety of intra-articular (IA) lidocaine plus adrenaline for improving peri-operative analgesia in anaesthetised dogs undergoing arthroscopy of the elbow. A solution of lidocaine (L) 1.98% plus adrenaline 1:100.000 was administered via the IA route and its safety evaluated in terms of cardio- neuro- and chondro-toxicity. No bradycardia or hypotension was recorded from induction to the last observational time point. Signs of toxicity of the nervous system could have been masked by the general anaesthesia but lidocaine concentrations detected in the blood were lower than those thought to be capable of producing toxicity. The assessment of in vitro chondrotoxicity showed a dose- and time-dependent effect of lidocaine on the viability of articular cells. Adrenaline appeared to reduce the chondrotoxicity of 1% lidocaine, following an exposure of up to 30 min

Electrochemical data on redox properties of human Cofilin-2 and its Mutant S3D

The reported data are related to a research paper entitled "Phosphorylated cofilin-2 is more prone to oxidative modifications on Cys39 and favors amyloid fibril formation" [1]. Info about the formation and redox properties of the disulfide bridge of a protein is quite difficult to obtain and only in a few cases was it possible to observe a cyclic voltammetry (CV) signal [2,3]. Human cofilin-2 contains two cysteines (Cys39 and Cys80) which can be oxidized in suitable conditions and form a disulfide bridge [1]. For this purpose, CV measurements were carried out on human cofilin-2 WT and its mutant S3D immobilized on a gold electrode coated by an anionic self-assembled monolayer (SAM), after a pre-oxidation time which was fundamental for observing a CV signal relating to the oxidation/reduction process of the disulfide bridge of the proteins. The data include CV curves obtained with and without electrochemical pre-oxidation and after oxidation with H2O2. In addition, the plot of the cathodic peak current vs. electrochemical pre-oxidation time and the pH dependence of the formal potential (E°’) are reported. The data obtained by CV measurements were used to determine the time required to form the disulfide bridge for the immobilized proteins and, consequently, to observe the CV signal, to calculate the E°’ values and analyse the pH dependence of E°’. The electrochemical data were provided which will be useful for further electrochemical investigations regarding proteins bearing disulfide bridge(s) or cysteines prone to oxidation

Gender Gap in Repartnering: The Role of Parental Status and Custodial Arrangements : Gender Gap in Repartnering

Objective: This study assesses whether parenthood influences repartnering for women and men and explores how repartnering is associated with parental status of the prospective partners. Background: Previous research has not demonstrated whether gender differences in repartnering are conditional on the presence of children. This study aims to better disentangle the specific gender differentials in repartnering probabilities conditional on parenthood and child custody status. Method: The analytical sample consists of 5,372 women and 3,375 men who reported at least one partnership dissolution in the British Understanding Society survey. Multilevel event history models with Markov Chain Monte Carlo simulations are used to estimate the probabilities of (a) finding a new partner and (b) finding a new childless partner or a new partner who has children. Results: The results suggest that mothers, and to a lesser extent fathers, are less likely to repartner than their childless counterparts. Among parents who have child custody, there emerges a distinct gender gap because mothers exhibit a significantly lower rate of repartnering than fathers. Finally, coresident single parents are relatively less likely to repartner with childless individuals, and single fathers more frequently form two-parent stepfamilies than do mothers. Conclusion: This suggests the presence of a gender divide in repartnering that is especially apparent when child custody is taken into account. The presence of children also reduces the possibility of forming unions with childless individuals

A serum metabolomics classifier derived from elderly patients with metastatic colorectal cancer predicts relapse in the adjuvant setting

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing

AGILE detection of delayed gamma-ray emission from GRB 080514B

GRB 080514B is the first gamma ray burst (GRB), since the time of EGRET, for which individual photons of energy above several tens of MeV have been detected with a pair-conversion tracker telescope. This burst was discovered with the Italian AGILE gamma-ray satellite. The GRB was localized with a cooperation by AGILE and the interplanetary network (IPN). The gamma-ray imager (GRID) estimate of the position, obtained before the SuperAGILE-IPN localization, is found to be consistent with the burst position. The hard X-ray emission observed by SuperAGILE lasted about 7 s, while there is evidence that the emission above 30 MeV extends for a longer duration (at least ~13 s). Similar behavior was seen in the past from a few other GRBs observed with EGRET. However, the latter measurements were affected, during the brightest phases, by instrumental dead time effects, resulting in only lower limits to the burst intensity. Thanks to the small dead time of the AGILE/GRID we could assess that in the case of GRB 080514B the gamma-ray to X-ray flux ratio changes significantly between the prompt and extended emission phase.Comment: A&A letters, in pres

Observation of the TeV gamma-ray source MGRO J1908+06 with ARGO-YBJ

The extended gamma ray source MGRO J1908+06, discovered by the Milagro air shower detector in 2007, has been observed for about 4 years by the ARGO-YBJ experiment at TeV energies, with a statistical significance of 6.2 standard deviations. The peak of the signal is found at a position consistent with the pulsar PSR J1907+0602. Parametrizing the source shape with a two-dimensional Gauss function we estimate an extension \sigma = 0.49 \pm 0.22 degrees, consistent with a previous measurement by the Cherenkov Array H.E.S.S.. The observed energy spectrum is dN/dE = 6.1 \pm 1.4 \times 10^-13 (E/4 TeV)^{-2.54 \pm 0.36} photons cm^-2 s^-1 TeV^-1, in the energy range 1-20 TeV. The measured gamma ray flux is consistent with the results of the Milagro detector, but is 2-3 times larger than the flux previously derived by H.E.S.S. at energies of a few TeV. The continuity of the Milagro and ARGO-YBJ observations and the stable excess rate observed by ARGO-YBJ along 4 years of data taking support the identification of MGRO J1908+06 as the steady powerful TeV pulsar wind nebula of PSR J1907+0602, with an integrated luminosity above 1 TeV about 1.8 times the Crab Nebula luminosity.Comment: 6 pages, accepted for pubblication by ApJ. Replaced to correct the author lis