Proinsulin attenuates the loss of vision and delays apoptosis of photoreceptors in a mouse model of retinitis pigmentosa.

34 p. 8 fig. 2 supl. fig.purpose. Retinitis pigmentosa (RP) is a heterogeneous group of inherited conditions that lead to blindness and for which there is no effective therapy. Apoptosis of photoreceptors is a common feature in animal models of the disease. Thus, the authors studied the therapeutic potential of proinsulin, an antiapoptotic molecule active during retinal development. methods. Transgenic mice expressing human proinsulin (hPi) in the skeletal muscle were generated in a mixed C57BL/6:SJL background and were back-crossed to a C57BL/6 background. Two independent lineages of transgenic mice were established in which hPi production in muscle was constitutive and not regulated by glucose levels. hPi levels in serum, muscle, and retina were determined with a commercial ELISA kit, visual function was evaluated by electroretinographic (ERG) recording, and programmed cell death was assessed by TUNEL. Immunohistochemistry was used to evaluate retinal structure preservation and oxidative damage. results. Transgenic expression of hPi in the rd10 retinal degeneration mouse model led to prolonged vision, as determined by ERG recording, in a manner that was related to the level of transgene expression. This attenuation of visual deterioration was correlated with a delay in photoreceptor apoptosis and with the preservation of retinal cytoarchitecture, particularly that of the cones. conclusions. These results provide a new basis for possible therapies to counteract retinitis pigmentosa and a new tool to characterize the mechanisms involved in the progress of retinal neurodegenerationSupported by Spanish Ministerio de Educación y Ciencia Grants SAF2001-1038, SAF2004-05870, and SAF2007-66175 (EJdlR, PdlV); BFU2004-02352 (FdP); SAF2005-01262 (FB); Spanish Ministerio de Sanidad y Consumo Grant RETIC RD-06 (FdP, FB); Comunidad de Madrid Grants 8.5-0019.1/2001 (EJdlR) and 08.5-0049/2003 and CCG06-UAH/BIO-0711 (PdlV); Fundación Médica Mutua Madrileña (EJdlR); and Fundaluce (PdlV). SC and NR-M were supported by postgraduate fellowships from the Ministerio de Educación y Ciencia, PB by a Ramón y Cajal contract from the Ministerio de Educación y Ciencia, AIA by a postdoctoral contract from the Fondo de Investigaciones Sanitarias, and VG-V by an I3P postdoctoral contract from the European Social FundPeer reviewe

Por Don Blas Francisco de Reyna Velmonte y Veneroso, en el pleyto con el Colegio de San Pablo de la Compañía de Jesus de esta ciudad de Granada, y con don Agustín Palavesin, vezino, y natural de la de Genova, y con Don Juan Mathias Chavarino, escrivano de Cámara de esta Real Chancillería, sobre la sucession de el mayorazgo que fundo Don Juan Pedro Veneroso, y el que fundò Bartolomè Veneroso, de los quales fue vltimo posseedor Don Juan Bartolomè Veneroso...

Inic. grab.Lugar y fecha de imp. probables deducidos del textoEn port. grab. xil. esc. de la Inquisición: "In hoc signo vinces"Texto a dos col.1342514v-5A-R

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational study

International audienceNo abstract availabl

Conjunctivitis in COVID-19 patients: frequency and clinical presentation

Purpose: The purpose of this study was to evaluate the frequency and clinical presentation of conjunctivitis in hospitalized patients with COVID-19. Methods: A cross-sectional study was conducted at the Hospital Clinico San Carlos of Madrid, Spain. A total of 301 subjects from the COVID admission unit with laboratory-confirmed SARS-CoV-2 infection were included. The presence and clinical characteristics of conjunctivitis were evaluated. Laboratory, radiological, and clinical results in patients with and without conjunctivitis stratified by sex were analyzed. Results: Of the 301 subjects included, 180 patients (59.8%) were male and the median age was 72 years (IQ 59–82). Overall, 35 patients (11.6%) were diagnosed with acute conjunctivitis. We found no relationship between the COVID-19 severity score and the presence of conjunctivitis (P = 0.17). However, conjunctivitis was more frequent in males with moderate clinical severity and in women classified as clinically mild. The natural history of the disease seems to be a rapid self-limited conjunctivitis that improves without treatment and does not affect visual acuity nor associate short-term complications. Conclusions: Approximately, 1 out of 10 hospitalized non-critical COVID-19 patients presents conjunctivitis during the disease. Compared with other viral conjunctivitis, we found distinctive clinical findings that could guide defining and differentiating conjunctivitis in COVID-19 patients

Por Don Blas Francisco de Reyna Velmonte y Veneroso, en el pleyto con el Colegio de San Pablo de la Compañía de Jesus de esta ciudad de Granada, y con don Agustín Palavesin, vezino, y natural de la de Genova, y con Don Juan Mathias Chavarino, escrivano de Cámara de esta Real Chancillería, sobre la sucession de el mayorazgo que fundo Don Juan Pedro Veneroso, y el que fundò Bartolomè Veneroso, de los quales fue vltimo posseedor Don Juan Bartolomè Veneroso... / [Lic. D. Fernando de la Muela Romero, Doct. D. Joseph de Reyna Infante]

Lugar y fecha de imp. probables deducidos del textoEn port. grab. xil. esc. de la Inquisición: "In hoc signo vinces"Texto a dos col.Fecha probable de imp.Sign.: A-R2Enc. Perg.Inic. grab