Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after short-term treatment with intravitreous bevacizumab

OBJECTIVE: Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits. METHODS: Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test. RESULTS: No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group. CONCLUSIONS: Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eye

Um caso atípico de esporotricose felina

A esporotricose é uma micose cutânea causada pelo fungo Sporothrix schenckii o qual pode infectar diferentes espécies animal e o homem. O objetivo desse trabalho é relatar um caso atípico de esporotricose num gato doméstico. Um gato de um ano de idade, sem raça definida, macho castrado, domiciliado com acesso à rua, apresentava um histórico de uma lesão cutânea ulcerativa de três meses na região escrotal, após a realização da orquiectomia. Na inspeção da região perianal foi evidenciada uma ferida exuberante única piogranulomatosa com áreas teciduais necrosadas. Não foi possível identificar orifício uretral. O gato apresentava obstrução uretral parcial, ocasionando grave retenção urinária. Sporothrix schenckii foi isolado da lesão. O tratamento com itraconazol oral por dois meses provou ser eficaz associado com a uretrostomia perineal

Meloxicam e prednisona: efeitos do tratamento oral de curto prazo sobre os níveis de pressão intra-ocular em cães

Para possível observação da hipertensão ocular com o uso de anti-inflamatórios, foram selecionados 28 cães da raça Beagle. Para avaliação da pressão intra-ocular antes do tratamento, no dia 0 (zero) todos os animais tiveram a pressão intra-ocular avaliada às 08 horas e às 16 horas. No dia seguinte dez cães receberam meloxicam na dose de 0,2 mg/kg, e 0,1mg/kg nos restantes quatro dias. Nove cães receberam prednisona na dose de 1,0 mg/kg durante cinco dias. Nove cães receberam somente porção de ração úmida. No quinto dia do tratamento todos os animais tiveram novamente a pressão intra-ocular avaliada às 08 horas e às 16 horas. Em todos os grupos, incluindo o grupo-controle, as maiores médias de pressão intra-ocular foram observadas no dia 5 (cinco). A diferença dos valores de pressão intra-ocular observada entre as medições das 08 horas e das 16 horas foi significativa, independente do tratamento e do dia considerado. O uso dos anti-inflamatórios esteroidal e não-esteroidal não foi capaz de causar hipertensão ocular e alguns fatores podem ser incriminados, como via de administração, dose e duração do tratamento utilizado, além da ausência de doença glaucomatosa nos cães selecionados.In order to observe a possible ocular hypertension associated with the use of anti-inflammatory drugs, 28 beagle dogs were selected. For evaluation of intraocular pressure before treatment, the totality of animals had their intraocular pressure measured at 8 a.m. and 4 p.m. on day 0 (zero). On the following day 10 animals received meloxican on dose of 0.2 mg/Kg and 0.1 mg/Kg on the four remaining days. Nine dogs received prednisone on dose of 1,0 mg/Kg during five days. Nine dogs received only wet feeding. On the fifth day of treatment the totality of dogs had their intraocular pressure measured at 8 a.m. and 4 p.m. For all groups, including control-group, the highest average values of intraocular pressure were observed on day 5 (five). The difference between the two evaluations of intra-ocular pressure (8 a.m. and 4 p.m) was significant, independent of treatment and of the considered day. The use of both steroidal or non-steroidal anti-inflammatory were not capable of causing ocular hypertension and some factors can be pointed out, such as route of administration, dosage and duration of therapy chosen, besides absence of glaucomatous disorder between the selected dogs

Increased transcription of transglutaminase 1 mediates neuronal death in in vitro models of neuronal stress and Aβ1–42-mediated toxicity

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The still under-investigated role of cognitive deficits in PML diagnosis

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

HIPK2 deficiency causes chromosomal instability by cytokinesis failure and increases tumorigenicity

HIPK2, a cell fate decision kinase inactivated in several human cancers, is thought to exert its oncosuppressing activity through its p53-dependent and -independent apoptotic function. However, a HIPK2 role in cell proliferation has also been described. In particular, HIPK2 is required to complete cytokinesis and impaired HIPK2 expression results in cytokinesis failure and tetraploidization. Since tetraploidy may yield to aneuploidy and chromosomal instability (CIN), we asked whether unscheduled tetraploidy caused by loss of HIPK2 might contribute to tumorigenicity. Here, we show that, compared to Hipk2+/+ mouse embryo fibroblasts (MEFs), hipk2-null MEFs accumulate subtetraploid karyotypes and develop CIN. Accumulation of these defects inhibits proliferation and spontaneous immortalization of primary MEFs whereas increases tumorigenicity when MEFs are transformed by E1A and Harvey-Ras oncogenes. Upon mouse injection, E1A/Ras-transformed hipk2-null MEFs generate tumors with genetic alterations resembling those of human cancers derived by initial tetraploidization events, such as pancreatic adenocarcinoma. Thus, we evaluated HIPK2 expression in different stages of pancreatic transformation. Importantly, we found a significant correlation among reduced HIPK2 expression, high grade of malignancy, and high nuclear size, a marker of increased ploidy. Overall, these results indicate that HIPK2 acts as a caretaker gene, whose inactivation increases tumorigenicity and causes CIN by cytokinesis failure

A New Orbiting Deployable System for Small Satellite Observations for Ecology and Earth Observation

In this paper, we present several study cases focused on marine, oceanographic, and atmospheric environments, which would greatly benefit from the use of a deployable system for small satellite observations. As opposed to the large standard ones, small satellites have become an effective and affordable alternative access to space, owing to their lower costs, innovative design and technology, and higher revisiting times, when launched in a constellation configuration. One of the biggest challenges is created by the small satellite instrumentation working in the visible (VIS), infrared (IR), and microwave (MW) spectral ranges, for which the resolution of the acquired data depends on the physical dimension of the telescope and the antenna collecting the signal. In this respect, a deployable payload, fitting the limited size and mass imposed by the small satellite architecture, once unfolded in space, can reach performances similar to those of larger satellites. In this study, we show how ecology and Earth Observations can benefit from data acquired by small satellites, and how they can be further improved thanks to deployable payloads. We focus on DORA—Deployable Optics for Remote sensing Applications—in the VIS to TIR spectral range, and on a planned application in the MW spectral range, and we carry out a radiometric analysis to verify its performances for Earth Observation studies

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz