Impact of blood sampling technique on reproducibility of viscoelastic coagulation monitor (VCM™) system test results in the neonate.

Purpose: To evaluate the reproducibility of the results of the viscoelastic coagulation test (VCT) performed with a new viscoelastic coagulation monitor (VCM™ – Entegrion) on native blood obtained ..

Graft Detachment After Descemet's Stripping Automated Endothelial Keratoplasty in Bullous Keratopathy and Fuchs Dystrophy

Descemet’s stripping automated endothelial keratoplasty (DSAEK) is a surgical technique for corneal transplantation in case of corneal decompensation. One of the main complications is graft detachment (GD) recoverable with Air Re-bubbling (ARB). The aim of this retrospective, interventional case series was to identify factors related to this complication in eyes operated for bullous keratopathy (BK) and Fuchs dystrophy (FD). We considered one-hundred patients who underwent DSAEK for BK or FD between January 2016 and October 2017 at Department of Ophthalmology, Policlinico Universitario of Bari, Italy. Studied parameters included physiological and pathological anamnesis of both donors and recipients and properties of donor’s lenticules and of the recipient’s corneas. Data was analyzed using One-way ANOVA with Tukey post hoc test and Chi-square test with Odds Ratio (OR) calculation. We grouped patients according to diagnosis. GD occurred in 9 eyes affected by BK and 19 by FD (p=0.003, OR = 0.25, 95% CI, 0.098-0.62). It was recovered with ARB. In BK, ARB correlated to complicated cataract extraction (p=0.04, OR = 7.83, 95% CI, 1.28 – 47.98) and aphakia (p=0.026, OR = 54.38, 95% CI, 2.51 - 11.76). In FD, ARB was associated to donor’s death for neoplasia (p=0.06, OR= 4.04, 95% CI, 1.06 – 15.37). No other differences were found. In conclusion, we could hypothesize that in FD patients, donor’s cancer therapy may play a role on altered corneal fibroblast metabolism, activating a synergetic effect between chemotherapy and genetic alteration of FD, which may lead to an altered adhesion of donor’s lenticule on recipient's stroma. In BK patients, complicated cataract extraction and aphakic status of recipients’ eye may contribute to altered adhesion of donor’s lenticule post-DSAEK

Graft Detachment After Descemet's Stripping Automated Endothelial Keratoplasty in Bullous Keratopathy and Fuchs Dystrophy

Descemet’s stripping automated endothelial keratoplasty (DSAEK) is a surgical technique for corneal transplantation in case of corneal decompensation. One of the main complications is graft detachment (GD) recoverable with Air Re-bubbling (ARB). The aim of this retrospective, interventional case series was to identify factors related to this complication in eyes operated for bullous keratopathy (BK) and Fuchs dystrophy (FD). We considered one-hundred patients who underwent DSAEK for BK or FD between January 2016 and October 2017 at Department of Ophthalmology, Policlinico Universitario of Bari, Italy. Studied parameters included physiological and pathological anamnesis of both donors and recipients and properties of donor’s lenticules and of the recipient’s corneas. Data was analyzed using One-way ANOVA with Tukey post hoc test and Chi-square test with Odds Ratio (OR) calculation. We grouped patients according to diagnosis. GD occurred in 9 eyes affected by BK and 19 by FD (p=0.003, OR = 0.25, 95% CI, 0.098-0.62). It was recovered with ARB. In BK, ARB correlated to complicated cataract extraction (p=0.04, OR = 7.83, 95% CI, 1.28 – 47.98) and aphakia (p=0.026, OR = 54.38, 95% CI, 2.51 - 11.76). In FD, ARB was associated to donor’s death for neoplasia (p=0.06, OR= 4.04, 95% CI, 1.06 – 15.37). No other differences were found. In conclusion, we could hypothesize that in FD patients, donor’s cancer therapy may play a role on altered corneal fibroblast metabolism, activating a synergetic effect between chemotherapy and genetic alteration of FD, which may lead to an altered adhesion of donor’s lenticule on recipient's stroma. In BK patients, complicated cataract extraction and aphakic status of recipients’ eye may contribute to altered adhesion of donor’s lenticule post-DSAEK

Targeting neurosteroid synthesis as a therapy for schizophrenia-related alterations induced by early psychosocial stress

Background Cogent evidence has shown that schizophrenia vulnerability is enhanced by psychosocial stress in adolescence, yet the underpinnings of this phenomenon remain elusive. One of the animal models that best capture the relationship between juvenile stress and schizophrenia is isolation rearing (IR). This manipulation, which consists in subjecting rats to social isolation from weaning through adulthood, results in neurobehavioral alterations akin to those observed in schizophrenia patients. In particular, IR-subjected rats display a marked reduction of the prepulse inhibition (PPI) of the startle reflex, which are posited to reflect imbalances in dopamine neurotransmission in the nucleus accumbens (NAcc). We recently documented that the key neurosteroidogenic enzyme 5α-reductase (5αR) plays an important role in the dopaminergic regulation of PPI; given that IR leads to a marked down-regulation of this enzyme in the NAcc, the present study was designed to further elucidate the functional role of 5αR in the regulation of PPI of IR-subjected rats. Methods We studied the impact of the prototypical 5αR inhibitor finasteride (FIN) on the PPI deficits and NAcc steroid profile of IR-subjected male rats, in comparison with socially reared (SR) controls. Results FIN (25–100 mg/kg, i.p.) dose-dependently countered IR-induced PPI reduction, without affecting gating integrity in SR rats. The NAcc and striatum of IR-subjected rats displayed several changes in neuroactive steroid profile, including a reduction in pregnenolone in both SR and IR-subjected groups, as well as a decrease in allopregnanolone content in the latter group; both effects were significantly opposed by FIN. Conclusions These results show that 5αR inhibition counters the PPI deficits induced by IR, possibly through limbic changes in pregnenolone and/or allopregnanolone concentrations

Inhibition of 17α-hydroxylase/C17,20 lyase reduces gating deficits consequent to dopaminergic activation

Cogent evidence points to the involvement of neurosteroids in the regulation of dopamine (DA) neurotransmission and signaling, yet the neurobiological bases of this link remain poorly understood. We previously showed that inhibition of 5α-reductase (5αR), a key neurosteroidogenic enzyme, attenuates the sensorimotor gating deficits induced by DA receptor activation, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. To extend these findings, the present study was aimed at the assessment of the role of other key neurosteroidogenic enzymes in PPI, such as 17α-hydroxylase/C17,20 lyase (CYP17A1), 3α- and 3β-hydroxysteroid dehydrogenase (HSD), in Sprague-Dawley rats. The PPI deficits induced by the DAergic non-selective agonist apomorphine (APO, 0.25 mg/kg, SC) were dose-dependently attenuated by the selective CYP17A1 inhibitor abiraterone (ABI, 10-50 mg/kg, IP) in a fashion akin to that of the 5αR inhibitor finasteride (FIN, 100 mg/kg, IP). These systemic effects were reproduced by intracerebroventricular injection of ABI (1 μg/1 μl), suggesting the involvement of brain CYP17A1 in PPI regulation. Conversely, the PPI disruption induced by APO was not significantly affected by the 3α- and 3β-HSD inhibitors indomethacin and trilostane. Given that CYP17A1 catalyzes androgen synthesis, we also tested the impact on PPI of the androgen receptor (AR) antagonist flutamide (10 mg/kg, IP). However, this agent failed to reverse APO-induced PPI deficits; furthermore, AR endogenous ligands testosterone and dihydrotestosterone failed to disrupt PPI. Collectively, these data highlight CYP17A1 as a novel target for antipsychotic-like action, and suggest that the DAergic regulation of PPI is modulated by androgenic neurosteroids, through AR-unrelated mechanisms

Positive allosteric modulation of GABAB receptors ameliorates sensorimotor gating in rodent models

This is the peer reviewed version of the following article: Frau, R., Bini, V., Pillolla, G., Malherbe, P., Pardu, A., Thomas, A. W., Devoto, P. and Bortolato, M. (2014), Positive Allosteric Modulation of GABAB Receptors Ameliorates Sensorimotor Gating in Rodent Models. CNS Neurosci Ther, 20: 679–684. doi:10.1111/cns.12261, which has been published in final form at http://doi.org/10.1111/cns.12261. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.BACKGROUND: Converging evidence points to the involvement of γ-amino-butyric acid B receptors (GABABRs) in the regulation of information processing. We previously showed that GABABR agonists exhibit antipsychotic-like properties in rodent models of sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. The therapeutic potential of these agents, however, is limited by their neuromuscular side effects; thus, in the present study we analyzed whether rac-BHFF, a potent GABABR positive allosteric modulator (PAM), could counter spontaneous and pharmacologically induced PPI deficits across various rodent models. METHODS: We tested the antipsychotic effects of rac-BHFF on the PPI deficits caused by the N-methyl-D-aspartate glutamate receptor antagonist dizocilpine, in Sprague-Dawley rats and C57BL/6 mice. Furthermore, we verified whether rac-BHFF ameliorated the spontaneous PPI impairments in DBA/2J mice. RESULTS: rac-BHFF dose-dependently countered the PPI deficits across all three models, in a fashion akin to the GABABR agonist baclofen and the atypical antipsychotic clozapine; in contrast with these compounds, however, rac-BHFF did not affect startle magnitude. CONCLUSIONS: The present data further support the implication of GABABRs in the modulation of sensorimotor gating, and point to their PAMs as a novel promising tool for antipsychotic treatment, with fewer side effects than GABABR agonists

Human endogenous retrovirus, HERV-P and HERV-R in pediatric leukemia patients

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Enlarged vascular foramina and lytic lesions in vertebral bodies: a diagnostic dilemma

Among the skeletal material from the sites of Alghero, Mesumundu and Sant’Antioco di Bisarcio (Sassari, Sardinia) and dated back to the period comprises between the 13th and the late 16th century 5 subadult individuals aged between 5 and 15 years and a mature male showed peculiar osteolytic phenomena of the vertebral bodies. These lesions have the appearance of enlarged vascular foramina, affecting several vertebrae mainly of the thoracic and lumbar spine, sometimes with involvement of the sacrum; on the same vertebral body several lesions are generally visible. In the literature similar features have been attributed to brucellosis or tuberculosis. As for the Sardinian skeletal material, an imaging study on the vertebrae of the adult individual was carried out in order to evaluate the appearance of the lesions within the body. Computed Tomography evidenced internal irregular elongated cavitations, sometimes joined together; erosive rounded lesions, whose presence is not detectable externally, were also showed. The molecular analysis has so far been performed on the subadult from Sant’Antioco di Bisarcio, but at initial analysis the DNA resulted degraded. Therefore, the nature of these lesions remains unclear, as it is not sure if they should be referred to tuberculosis, brucellosis or other pathological conditions [hemolytic anemias (eg. Thalassemia), lymphomas, multiple myeloma and infection by Echinococcus]. Further molecular analyses will be carried out on the remains belonging to the other five individuals in an attempt to clarify the etiology of the above mentioned lesions

Monoamine oxidase A and A/B knockout mice display autistic-like features

This is the published version, also available electronically from http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8876069&fileId=S1461145712000715Converging lines of evidence show that a sizable subset of autism-spectrum disorders (ASDs) is characterized by increased blood levels of serotonin (5-hydroxytryptamine, 5-HT), yet the mechanistic link between these two phenomena remains unclear. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages. Here we show that both mutant lines exhibit numerous behavioural hallmarks of ASDs, such as social and communication impairments, perseverative and stereotypical responses, behavioural inflexibility, as well as subtle tactile and motor deficits. Furthermore, both MAOA and A/B KO mice displayed neuropathological alterations reminiscent of typical ASD features, including reduced thickness of the corpus callosum, increased dendritic arborization of pyramidal neurons in the prefrontal cortex and disrupted microarchitecture of the cerebellum. The severity of repetitive responses and neuropathological aberrances was generally greater in MAOA/B KO animals. These findings suggest that the neurochemical imbalances induced by MAOA deficiency (either by itself or in conjunction with lack of MAOB) may result in an array of abnormalities similar to those observed in ASDs. Thus, MAOA and A/B KO mice may afford valuable models to help elucidate the neurobiological bases of these disorders and related neurodevelopmental problem