Ceratite aguda por herpes zoster: um relato de caso/ Acute zoster keratitis: a case report

Introdução: O vi?rus varicela-zo?ster (VZV), ou herpesvi?rus tipo 3, causa duas síndromes virais distintas: varicela (catapora) e herpes-zo?ster. O principal fator desencadeante do herpes zo?ster e? a idade avançada, seguida por imunossupressão, trauma e irradiac?a?o. O herpes-zo?ster ofta?lmico (HZO) se inicia com o pro?dromo de febre, cefaleia e fadiga, e, posteriormente, evolui com manifestações cutâneas localizadas no derma?tomo inervado pelo ramo acometido. O exantema inicia-se como erupc?a?o maculopapular, evoluindo para vesículas de conteúdo claro que tornam-se pu?stulas flavas e, posteriormente, crostas. Alguns sinais são característicos do acometimento do ramo trigêmio, como o sinal de Hutchinson (vesi?culas e pústulas na ponta do nariz). O tratamento da fase aguda do HZO e? sistêmico, com o uso de antivirais orais no paciente imunocompetente e tópicos quando há ceratite. Relato de caso: Paciente de 82 anos, proveniente de Onça de Pitangui, MG. Apresentou-se em abril/2018 à UBS queixando-se de hiperemia, dor conjuntival e secreção ocular flava, além de lesão pruriginosa em região frontal. É firmado o diagnóstico de conjuntivite bacteriana e iniciado tratamento com Cilodex®. Após 3 dias, paciente evolui com aparecimento de pústulas em região frontal e dorso nasal. Encaminhado ao hospital em Belo Horizonte, foi efetuado diagnóstico de ceratite herpética por VZV. Discussão: O paciente avaliado apresenta fatores desencadeantes, como exposição solar e idade que corroboram com o desenvolvimento de HZO. Sintomas prodrômicos não foram encontrados no caso, apesar de serem frequentes nessa patologia. O sinal de Hutchinson, indicativo de acometimento do ramo nasociliar do nervo oftálmico, foi o direcionador para a possibilidade diagnostica de HZO e para posterior investigação especifica de ceratite herpética. O tratamento deve ser introduzido precocemente para evitar complicações e sequelas.  Conclusão: A ceratite herpética por VZV é, portanto, um quadro desafiador no aspecto de identificação e tratamento. Faz-se assim importante o relato do caso, para que possa-se ter maior conhecimento sobre a lesão e menos complicações, como danos oculares irreversíveis. O tratamento é simples e, quando adequado, evita perda visual permanente

Systemic AA amyloidosis caused by inflammatory hepatocellular adenoma

To the Editor: Amyloid A (AA) systemic amyloidosis is a complication of chronic inflammatory diseases that is caused by the deposition of insoluble aggregates of cleaved N-terminal fragments of serum amyloid A (SAA) protein in tissues and organs throughout the body. Under physiologic conditions, SAA protein is produced by hepatocytes during the acute inflammatory phase in response to various cytokines such as interleukin-6. SAA is also overexpressed by neoplastic hepatocytes in inflammatory hepatocellular adenomas, a specific molecular subtype of benign liver tumors

Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle

The molecular mechanisms by which aging affects stem cell number and function are poorly understood. Murine data have implicated cellular senescence in the loss of muscle stem cells with aging. Here, using human cells and by carrying out experiments within a strictly pre-senescent division count, we demonstrate an impaired capacity for stem cell self-renewal in elderly muscle. We link aging to an increased methylation of the SPRY1 gene, a known regulator of muscle stem cell quiescence. Replenishment of the reserve cell pool was modulated experimentally by demethylation or siRNA knockdown of SPRY1. We propose that suppression of SPRY1 by age-associated methylation in humans inhibits the replenishment of the muscle stem cell pool, contributing to a decreased regenerative response in old age. We further show that aging does not affect muscle stem cell senescence in humans

Ectodermal Influx and Cell Hypertrophy Provide Early Growth for All Murine Mammary Rudiments, and Are Differentially Regulated among Them by Gli3

Mammary gland development starts in utero with one or several pairs of mammary rudiments (MRs) budding from the surface ectodermal component of the mammalian embryonic skin. Mice develop five pairs, numbered MR1 to MR5 from pectoral to inguinal position. We have previously shown that Gli3Xt-J/Xt-J mutant embryos, which lack the transcription factor Gli3, do not form MR3 and MR5. We show here that two days after the MRs emerge, Gli3Xt-J/Xt-J MR1 is 20% smaller, and Gli3Xt-J/Xt-J MR2 and MR4 are 50% smaller than their wild type (wt) counterparts. Moreover, while wt MRs sink into the underlying dermis, Gli3Xt-J/Xt-J MR4 and MR2 protrude outwardly, to different extents. To understand why each of these five pairs of functionally identical organs has its own, distinct response to the absence of Gli3, we determined which cellular mechanisms regulate growth of the individual MRs, and whether and how Gli3 regulates these mechanisms. We found a 5.5 to 10.7-fold lower cell proliferation rate in wt MRs compared to their adjacent surface ectoderm, indicating that MRs do not emerge or grow via locally enhanced cell proliferation. Cell-tracing experiments showed that surface ectodermal cells are recruited toward the positions where MRs emerge, and contribute to MR growth during at least two days. During the second day of MR development, peripheral cells within the MRs undergo hypertrophy, which also contributes to MR growth. Limited apoptotic cell death counterbalances MR growth. The relative contribution of each of these processes varies among the five MRs. Furthermore, each of these processes is impaired in the absence of Gli3, but to different extents in each MR. This differential involvement of Gli3 explains the variation in phenotype among Gli3Xt-J/Xt-J MRs, and may help to understand the variation in numbers and positions of mammary glands among mammals

Microtubules as Platforms for Assaying Actin Polymerization In Vivo

The actin cytoskeleton is continuously remodeled through cycles of actin filament assembly and disassembly. Filaments are born through nucleation and shaped into supramolecular structures with various essential functions. These range from contractile and protrusive assemblies in muscle and non-muscle cells to actin filament comets propelling vesicles or pathogens through the cytosol. Although nucleation has been extensively studied using purified proteins in vitro, dissection of the process in cells is complicated by the abundance and molecular complexity of actin filament arrays. We here describe the ectopic nucleation of actin filaments on the surface of microtubules, free of endogenous actin and interfering membrane or lipid. All major mechanisms of actin filament nucleation were recapitulated, including filament assembly induced by Arp2/3 complex, formin and Spir. This novel approach allows systematic dissection of actin nucleation in the cytosol of live cells, its genetic re-engineering as well as screening for new modifiers of the process

Aging Hallmarks: the benefits of physical exercise

World population has been continuously increasing and progressively aging. Aging is characterized by a complex and intraindividual process associated with nine major cellular and molecular hallmarks, namely, genomic instability, telomere attrition, epigenetic alterations, a loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. This review exposes the positive antiaging impact of physical exercise at the cellular level, highlighting its specific role in attenuating the aging effects of each hallmark. Exercise should be seen as a polypill, which improves the health-related quality of life and functional capabilities while mitigating physiological changes and comorbidities associated with aging. To achieve a framework of effective physical exercise interventions on aging, further research on its benefits and the most effective strategies is encouraged

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field