Cambios fisiológicos de la córnea en respuesta al uso de ortoqueratología nocturna

Tesis de la Universidad Complutense de Madrid, Escuela Universitaria de Óptica, Departamento de Óptica II (Optometría y Visión), leída el 12-11-2010Depto. de Optometría y VisiónFac. de Óptica y OptometríaTRUEpu

Biomechanical properties in corneal refractive therapy during adaptation period and after treatment interruption: A pilot study

AbstractPurposeTo evaluate the potential influence and treatment-related changes of the corneal biomechanical properties (BMP) measured with the Ocular Response Analyzer (ORA, Reichert, Depew, NY) 15-days and 1-month after the initiation and cessation of corneal refractive therapy (CRT).MethodsTwenty-four young healthy subjects (24.04±3.19 years) participated in two different experiments. In the first one (#1), twelve right eyes from 12 subjects who were fitted with CRT lenses were evaluated after 15 days and 1 month of lens wear. In the second trial (#2) 12 subjects who had been wearing CRT lenses for a period of 1 year were evaluated at 15 days and 1 month after treatment interruption.ResultsThere was no statistically significant correlation between baseline BMP and absolute values of structural corneal parameters at 15 and 30 days treatment, and also when these variables were normalized according to the targeted refraction. In experiment #1, Corneal hysteresis (CH) reduction was observed over the time of treatment (p=0.019), but no significant differences were observed in the Corneal Resistance Factor (CRF) values. In addition, CRF reduction significantly correlated with spherical equivalent refraction (r=0.597; p=0.044), but no correlation was observed between CH or CRF reduction and the spherical component of the refraction. In experiment #2, no significant changes in CH or CRF were found initially after lens wear interruption, but a trend to increase was observed thereafter.ConclusionCH decreases during onset of the CRT after 30 days of lens wear. Such changes seem to be reversible after cessation of contact lens wear following 1 year of treatment. Corneal biomechanics, however, do not predict the outcomes of CRT in clinical setting although with the data obtained some correlative tendencies were observed that may merit further investigation

Tear Film Osmolarity in Response to Long-Term Orthokeratology Treatment

Purpose: To compare tear film osmolarity (TFO) measurements in non-contact lens (CL) wearers and wearers of hydrogel or overnight orthokeratology (OK) CLs, and to assess possible effects of long-term OK on TFO. Methods: Overall, 108 subjects with moderate myopia participated in 2 experiments, and TFO was measured using the TearLab osmolarity system. In experiment 1, TFO measurements were made in 77 right eyes of 23 non-CL wearers, 26 hydrogel wearers, and 28 OK wearers. Subjects in the last 2 groups had worn their CL for at least 3 years. In experiment 2, 31 individuals (habitual soft CL wearers) were enrolled for prospective long-term follow-up of OK treatment. These subjects were fitted with Paragon-CRT (n=16) or Seefree (n=15) lenses, and TFO readings were taken at baseline and after 1 month and 1 year of lens wear and after 1 month of OK treatment interruption. Results: Values of TFO were within the normal limits in all 3 subject groups, although significantly lower osmolarities (P<0.01) were observed in non-CL wearers (281.7+/-5.9 mOsm/L) compared with hydrogel (291+/-16.5 mOsm/L) or OK lens wearers (301.7+/-10.8 mOsm/L). In experiment 2, TFO differed significantly at baseline between the Paragon-CRT and Seefree groups (P<0.05), and a significant decrease in TFO compared with baseline (P<0.01) was observed in the Paragon-CRT group after 1 month of cessation of lens wear. Conclusion: Higher TFO values were observed in lens wearers (hydrogel or OK) than non-CL wearers. After interruption of OK treatment, TFO returned to similar values to those found in non-CL wearers

Short-term Effects of Overnight Orthokeratology on Corneal Sub-basal Nerve Plexus Morphology and Corneal Sensitivity

Objective: To assess the effects of a short period of orthokeratology (OK) on corneal subbasal nerve plexus (SBNP) morphology and corneal sensitivity. Methods: Measurements were made in 56 right eyes of 56 subjects with low-to-moderate myopia who wore 2 OK lens designs (Group CRT: HDS 100 Paragon CRT, n=35; Group SF: Seefree; n=21) for a period of 1 month and in 15 right eyes of noncontact lens wearers as controls. The variables determined in each participant were corneal sensitivity using a Cochet-Bonnet esthesiometer and 12 SBNP variables determined on laser scanning confocal microscopy images using 3 different software packages. Correlation between SBNP architecture and corneal sensitivity was also examined. Results: Few changes were observed over the 1-month period in the variables examined in the OK treatment and control groups. However, significant reductions were detected over time in the number of nerves in the central cornea in the groups CRT (P=0.029) and SF (P=0.043) and in central corneal sensitivity in CRT (P=0.047) along with significant increases in central and midperipheral corneal Langerhans cell counts in SF (P=0.001 and 0.048, respectively). Conclusions: This study provides useful data to better understand the anatomical changes induced by OK in corneal SBNP. The different response observed to the 2 OK lens designs requires further investigation

Long-Term Impacts of Orthokeratology Treatment on Sub-Basal Nerve Plexus and Corneal Sensitivity Responses and Their Reversibility

Purpose: To examine the effects of one year of overnight orthokeratology (OK) treatment on the sub-basal nerve plexus (SBNP) and corneal sensitivity and to assess the reversibility of these effects one month after treatment interruption. Methods: Thirty-two subjects with low-moderate myopia underwent OK treatment for one year. Fifteen non-contact lens wearers served as controls. At the time points baseline, one year of treatment, and one month after removing the OK lenses, two tests were conducted: corneal sensitivity (Cochet-Bonnet esthesiometer) and SBNP imaging by in vivo confocal microscopy. Results: In participants wearing OK lenses, significant reductions over the year were produced in SBNP nerve density (P=0.001 and P=0.006) and number of nerves (P<0.001 and P=0.001) in the central and mid-peripheral cornea, respectively. Differences over the year were also detected in central objective tortuosity (P=0.002). After lens removal, baseline values of nerve density (P=0.024 and P=0.001) and number of nerves (P=0.021 and P<0.001) for the central and mid-peripheral cornea, respectively, were not recovered. At one month post-treatment, a difference was observed from one-year values in central corneal sensitivity (P=0.045) and mid-peripheral Langerhans cell density (P=0.033), and from baseline in mid-peripheral objective tortuosity (P=0.049). Direct correlation was detected at one year between nerve density and tortuosity both in the central (P<0.01; r=0.69) and mid-peripheral cornea (P<0.01; r=0.76). Conclusions: Long-term OK treatment led to reduced SBNP nerve density and this was directly correlated with corneal tortuosity. After one month of treatment interruption, nerve density was still reduced

Mutation S110L of H1N1 Influenza Virus Hemagglutinin: A Potent Determinant of Attenuation in the Mouse Model

Characterization of a pandemic 2009 H1N1 influenza virus isolated from a fatal case patient (F-IAV), showed the presence of three different mutations; potential determinants of its high pathogenicity that were located in the polymerase subunits (PB2 A221T and PA D529N) and the hemagglutinin (HA S110L). Recombinant viruses containing individually or in combination the polymerase mutations in the backbone of A/California/04/09 (CAL) showed that PA D529N was clearly involved in the increased pathogenicity of the F-IAV virus. Here, we have evaluated the contribution of HA S110L to F-IAV pathogenicity, through introduction of this point mutation in CAL recombinant virus (HA mut). The HA S110L protein has similar pH stability, comparable mobility, and entry properties both in human and mouse cultured cells that wild type HA. The change HA S110L leads to a non-significant trend to reduce the replication capacity of influenza virus in tissue culture, and HA mut is better neutralized than CAL virus by monoclonal and polyclonal antibodies against HA from CAL strain. In addition, recombinant viruses containing HA S110L alone or in combination with polymerase mutations considerably increased the LD50 in infected mice. Characterization of the lungs of HA mut infected animals showed reduced lung damage and inflammation compared with CAL infected mice. Accordingly, lower virus replication, decreased presence in bronchioli and parenchyma and lower leukocytes and epithelial infected cells were found in the lungs of HA mut-infected animals. Our results indicate that, mutation HA S110L constitutes a determinant of attenuation and suggest that its interaction with components of the respiratory tract mucus and lectins, that play an important role on influenza virus outcome, may constitute a physical barrier impeding the infection of the target cells, thus compromising the infection outcome

Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response

Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications. Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection. DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection. A particular increase in H3K79 methylation was observed and the use of an inhibitor of the specific H3K79 methylase, Dot1L enzyme, or its silencing, increased influenza virus replication. The antiviral response was reduced in conditions of Dot1L downregulation, since decreased nuclear translocation of NF-kB complex, and IFN-β, Mx1 and ISG56 expression was detected. The data suggested a control of antiviral signaling by methylation of H3K79 and consequently, influenza virus replication was unaffected in IFN pathway-compromised, Dot1L-inhibited cells. H3K79 methylation also controlled replication of another potent interferon-inducing virus such as vesicular stomatitis virus, but did not modify amplification of respiratory syncytial virus that poorly induces interferon signaling. Epigenetic methylation of H3K79 might have an important role in controlling interferon-induced signaling against viral pathogens

hCLE/RTRAF-HSPC117-DDX1-FAM98B: A New Cap-Binding Complex That Activates mRNA Translation

hCLE/C14orf166/RTRAF, DDX1, and HSPC117 are components of cytoplasmic mRNA-transporting granules kinesin-associated in dendrites. They have also been found in cytoplasmic ribosome-containing RNA granules that transport specific mRNAs halted for translation until specific neuronal signals renders them accessible to the translation machinery. hCLE associates to DDX1, HSPC117, and FAM98B in HEK293T cells and all four proteins bind to cap analog-containing resins. Competition and elution experiments indicate that binding of hCLE complex to cap resins is independent of eIF4E; the cap-binding factor needed for translation. Purified hCLE free of its associated proteins binds cap with low affinity suggesting that its interacting proteins modulate its cap association. hCLE silencing reduces hCLE accumulation and that of its interacting proteins and decreases mRNA translation. hCLE-associated RNAs have been isolated and sequenced; RNAs involved in mRNA translation are specifically associated. The data suggest that RNA granules may co-transport RNAs encoding proteins involved in specific functions together with RNAs that encode proteins needed for the translation of these specific RNAs and indicate an important role for hCLE modulating mRNA translation

ISG15 Regulates Peritoneal Macrophages Functionality against Viral Infection

Upon viral infection, the production of type I interferon (IFN) and the subsequent upregulation of IFN stimulated genes (ISGs) generate an antiviral state with an important role in the activation of innate and adaptive host immune responses. The ubiquitin-like protein (UBL) ISG15 is a critical IFN-induced antiviral molecule that protects against several viral infections, but the mechanism by which ISG15 exerts its antiviral function is not completely understood. Here, we report that ISG15 plays an important role in the regulation of macrophage responses. ISG152/2 macrophages display reduced activation, phagocytic capacity and programmed cell death activation in response to vaccinia virus (VACV) infection. Moreover, peritoneal macrophages from mice lacking ISG15 are neither able to phagocyte infected cells nor to block viral infection in co-culture experiments with VACV-infected murine embryonic fibroblast (MEFs). This phenotype is independent of cytokine production and secretion, but clearly correlates with impaired activation of the protein kinase AKT in ISG15 knock-out (KO) macrophages. Altogether, these results indicate an essential role of ISG15 in the cellular immune antiviral response and point out that a better understanding of the antiviral responses triggered by ISG15 may lead to the development of therapies against important human pathogensThis work was supported by grants from the Spanish Ministry of Health FIS2011-00127, Comunidad de Madrid UAM-CM-CCG10-4911 and UAM-Banco de Santander to SG. This work was also partly supported by NIAID grant U19AI083025 and by CRIP (Center for Research on Influenza Pathogenesis, HHSN266200700010C), a NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS) to AGS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Medicamentos bucofaríngeos de no prescripción médica obligatoria

El farmacéutico, como profesional sanitario, juega un importante papel para garantizar el buen uso de los medicamentos. Merece especial atención la utilización de los antibióticos y los medicamentos bucofaríngeos de no prescripción médica ante una dolencia bucofaríngea, pues el paciente en la mayoría de los casos no utiliza o utiliza mal el fármaco necesario para su afección. Es aquí donde el profesional sanitario valorara el uso de uno u otro dependiendo de la patología y derivando si así se precisara al médico. Se analizara además si es adecuado su régimen legal y que opciones tiene el farmacéutico en el caso de que los medicamentos bucofaríngeos de origen industrial no solucionaran el síntoma menor del paciente. Para ello nos basamos en el test diagnóstico denominado Streptotest y de nuestra experiencia en las prácticas tuteladas donde se desarrolló un cuestionario de siete preguntas cerradas en cinco oficinas de farmacias diferentes de la Comunidad de Madrid. En vista de los resultados obtenidos, pudimos dar respuesta a los objetivos de trabajo, quedando expuestos a continuación